Article(id=1236731781425189256, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236731777142804746, articleNumber=null, orderNo=null, doi=10.20251/j.cnki.1003-3734.2025.17.011, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=1736784000000, acceptedDateStr=2025-01-14, onlineDate=1772789434056, onlineDateStr=2026-03-06, pubDate=1757865600000, pubDateStr=2025-09-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1772789434056, onlineIssueDateStr=2026-03-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1772789434056, creator=13701087609, updateTime=1772789434056, updator=13701087609, issue=Issue{id=1236731777142804746, tenantId=1146029695717560320, journalId=1235980733773295621, year='2025', volume='34', issue='17', pageStart='1793', pageEnd='1904', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=0, createTime=1772789433036, creator=13701087609, updateTime=1772801868692, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1236783936152596961, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236731777142804746, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1236783936152596962, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236731777142804746, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1858, endPage=1864, ext={EN=ArticleExt(id=1236731781718790562, articleId=1236731781425189256, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=Anti-inflammatory and anti-swelling active fraction of Stellera chamaejasme Daphne odora and its mechanism of action, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective:

To screen the anti-inflammatory and anti-swelling active fraction of Stellera chamaejasme Daphne odora, and to preliminarily explore its pharmacodynamics and mechanism of action.

Methods:

The toe swelling model was established in SD rats. The toe swelling, serum inflammatory factors and superoxide dismutase (SOD) activity were detected by daubing different extracts of Daphne odora chamaejasme and its ointment.

Results:

The water extract and ethanol precipitation of the drug had better anti-inflammatory and detumescence effect. The content was objective and the extraction process was simple. The 80% ethanol extract showed good anti-inflammatory and detumescence activity, but the drug activity was not as good as the former extract. Two types of extracts were formulated into an ointment for the aforementioned model experiments. The results indicated that, compared to the model group, the ointment significantly inhibited the swelling degree of inflammatory paw edema induced by carrageenan in rats. The serum samples of the experimental animals were analyzed for IL-1β and other inflammatory factors. Compared with the model group, the anti-inflammatory effect of the ointment was supported by IL-1β levels and the observations from tissue pathology sections. The activity of SOD was increased.

Conclusion:

Extract A and extract B are the effective parts of anti-inflammation and anti-swelling of Stellera chamaejasme Daphne odora.

, correspAuthors=NASHENGSANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=WURINILE, JIMUSI, NASHENGSANG), CN=ArticleExt(id=1236731784554140169, articleId=1236731781425189256, tenantId=1146029695717560320, journalId=1235980733773295621, language=CN, title=瑞香狼毒抗炎消肿有效部位及其作用机制研究, columnId=1236330556003242277, journalTitle=中国新药杂志, columnName=实验研究, runingTitle=null, highlight=null, articleAbstract=
目的:

筛选瑞香狼毒的抗炎消肿有效部位,并初步探讨其作用机制。

方法:

建立SD大鼠足趾肿胀模型,涂抹瑞香狼毒不同提取物及其膏剂检测动物足趾肿胀度、血清炎症因子水平及超氧化物歧化酶(superoxide dismutase,SOD)活性。

结果:

瑞香狼毒水提醇沉部位具有良好的抗炎消肿作用,且含量可观,提取过程简单;其次为瑞香狼毒80%醇提物显示出良好的抗炎消肿活性,但成药性不及水提醇沉部位。2种提取物制成软膏剂进行上述模型实验表明,与模型组比较,瑞香软膏能显著抑制角叉菜胶致大鼠炎性足肿胀的肿胀度,实验动物血清学分析白细胞介素-1β等炎症因子水平以及组织病理切片观察结果验证了该膏剂的抗炎作用。

结论:

本研究筛选出瑞香狼毒抗炎消肿有效部位为提取物A及提取物B,且2种提取物混合制作的瑞香软膏具有较强的炎症抑制作用。

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*那生桑,男,教授,研究方向:蒙药学。E-mail:
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乌日尼乐,女,药师,研究方向:临床蒙药学。E-mail:

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与空白组比较,a:P<0.01

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与模型组比较,a:P<0.05,b:P<0.01;与空白组比较,c:P<0.05,d:P<0.01

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黑色箭头:炎症细胞浸润;黄色箭头:滑膜细胞增生

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组别剂量/g不同时间足趾肿胀度
0.5 h1 h2 h4 h6 h10 h
模型组9.52±0.38c9.76±0.45c10.44±0.64c10.41±0.57c10.11±0.41c9.95±0.92c
空白组5.92±0.27b5.67±0.31b5.73±0.47b5.81±0.38b5.88±0.17b5.74±0.33b
阴性对照组1.09.08±0.31a9.09±0.5410.11±0.3310.16±0.319.77±0.569.46±0.42
阳性对照组1.08.43±0.45a9.01±0.75a9.71±0.65a9.82±0.43a9.50±0.51a9.36±0.62
提取物A组0.0749.03±0.31a9.25±0.4710.29±0.5610.11±0.729.61±0.629.03±0.61
提取物B组0.0138.88±0.479.10±0.41a9.88±0.649.72±0.37a9.55±0.46a8.64±0.34b
提取物C组0.0219.35±0.569.53±0.5010.21±0.5910.44±0.689.54±0.47a9.35±0.57
提取物D组0.0019.04±0.599.34±0.5910.22±0.5610.28±0.579.61±0.419.36±0.71
), ArticleFig(id=1236792934201348869, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1236731781425189256, language=CN, label=表1, caption=

瑞香狼毒各提取物对大鼠足肿胀度的影响

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组别剂量/g不同时间足趾肿胀度
0.5 h1 h2 h4 h6 h10 h
模型组9.52±0.38c9.76±0.45c10.44±0.64c10.41±0.57c10.11±0.41c9.95±0.92c
空白组5.92±0.27b5.67±0.31b5.73±0.47b5.81±0.38b5.88±0.17b5.74±0.33b
阴性对照组1.09.08±0.31a9.09±0.5410.11±0.3310.16±0.319.77±0.569.46±0.42
阳性对照组1.08.43±0.45a9.01±0.75a9.71±0.65a9.82±0.43a9.50±0.51a9.36±0.62
提取物A组0.0749.03±0.31a9.25±0.4710.29±0.5610.11±0.729.61±0.629.03±0.61
提取物B组0.0138.88±0.479.10±0.41a9.88±0.649.72±0.37a9.55±0.46a8.64±0.34b
提取物C组0.0219.35±0.569.53±0.5010.21±0.5910.44±0.689.54±0.47a9.35±0.57
提取物D组0.0019.04±0.599.34±0.5910.22±0.5610.28±0.579.61±0.419.36±0.71
), ArticleFig(id=1236792934297817865, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1236731781425189256, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别不同时间大鼠足趾离心远端肿胀度(剂量:1 mL·跖-1
0.5 h1 h2 h4 h6 h
模型组7.22±0.31c7.95±0.50c9.03±0.68c8.84±0.76c8.76±0.64c
阴性组6.72±0.34a7.26±0.538.51±0.808.87±0.568.07±0.51a
阳性组6.76±0.38a7.15±0.738.33±0.598.13±0.617.73±0.61b
低剂量组6.76±0.37a7.12±0.33b8.48±0.42a8.29±0.45a7.94±0.44a
高剂量组6.93±0.337.03±0.31b8.19±0.28a8.55±0.567.98±0.25a
空白组5.61±0.27b5.97±0.25b5.81±0.34b5.73±0.13b5.70±0.35b
), ArticleFig(id=1236792935757435662, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1236731781425189256, language=CN, label=表2, caption=

瑞香软膏对大鼠足肿胀的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别不同时间大鼠足趾离心远端肿胀度(剂量:1 mL·跖-1
0.5 h1 h2 h4 h6 h
模型组7.22±0.31c7.95±0.50c9.03±0.68c8.84±0.76c8.76±0.64c
阴性组6.72±0.34a7.26±0.538.51±0.808.87±0.568.07±0.51a
阳性组6.76±0.38a7.15±0.738.33±0.598.13±0.617.73±0.61b
低剂量组6.76±0.37a7.12±0.33b8.48±0.42a8.29±0.45a7.94±0.44a
高剂量组6.93±0.337.03±0.31b8.19±0.28a8.55±0.567.98±0.25a
空白组5.61±0.27b5.97±0.25b5.81±0.34b5.73±0.13b5.70±0.35b
), ArticleFig(id=1236792935874876179, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1236731781425189256, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别炎症因子水平(剂量:1 mL·跖-1
TNF-αIL-1βSODPGE-2
空白组91.17±22.8716.57±6.1910.69±2.8516.55±7.60
阳性组72.06±45.46b24.01±2.94a64.54±21.6227.48±13.83
模型组198.74±87.88d40.37±2.61d66.31±44.32d35.53±8.38c
低剂量组161.18±47.7433.47±15.22111.24±19.93a18.75±10.64a
高剂量组74.52±34.54b22.83±12.81a84.18±15.1716.36±7.27a
), ArticleFig(id=1236792935954567957, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1236731781425189256, language=CN, label=表3, caption=

瑞香软膏对大鼠模型血清炎症因子水平及总SOD活性的影响

, figureFileSmall=null, figureFileBig=null, tableContent=
组别炎症因子水平(剂量:1 mL·跖-1
TNF-αIL-1βSODPGE-2
空白组91.17±22.8716.57±6.1910.69±2.8516.55±7.60
阳性组72.06±45.46b24.01±2.94a64.54±21.6227.48±13.83
模型组198.74±87.88d40.37±2.61d66.31±44.32d35.53±8.38c
低剂量组161.18±47.7433.47±15.22111.24±19.93a18.75±10.64a
高剂量组74.52±34.54b22.83±12.81a84.18±15.1716.36±7.27a
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瑞香狼毒抗炎消肿有效部位及其作用机制研究
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乌日尼乐 1, 3 , 吉木斯 2 , 那生桑 1, *
中国新药杂志 | 实验研究 2025,34(17): 1858-1864
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中国新药杂志 | 实验研究 2025, 34(17): 1858-1864
瑞香狼毒抗炎消肿有效部位及其作用机制研究
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乌日尼乐1, 3 , 吉木斯2, 那生桑1, *
作者信息
  • 1内蒙古医科大学蒙医药学院,呼和浩特 010110
  • 2呼和浩特市蒙医中医医院,呼和浩特 010110
  • 3林西县医院,赤峰 024000
  • 乌日尼乐,女,药师,研究方向:临床蒙药学。E-mail:

通讯作者:

*那生桑,男,教授,研究方向:蒙药学。E-mail:
Anti-inflammatory and anti-swelling active fraction of Stellera chamaejasme Daphne odora and its mechanism of action
WURINILE1, 3 , JIMUSI2, NASHENGSANG1, *
Affiliations
  • 1Inner Mongolia Medical University, Hohhot 010110, China
  • 2Hohhot Mongolian Medicine Hospital of Traditional Chinese Medicine, Hohhot 010110, China
  • 3Linxi County Hospital, Chifeng 024000, China
出版时间: 2025-09-15 doi: 10.20251/j.cnki.1003-3734.2025.17.011
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目的:

筛选瑞香狼毒的抗炎消肿有效部位,并初步探讨其作用机制。

方法:

建立SD大鼠足趾肿胀模型,涂抹瑞香狼毒不同提取物及其膏剂检测动物足趾肿胀度、血清炎症因子水平及超氧化物歧化酶(superoxide dismutase,SOD)活性。

结果:

瑞香狼毒水提醇沉部位具有良好的抗炎消肿作用,且含量可观,提取过程简单;其次为瑞香狼毒80%醇提物显示出良好的抗炎消肿活性,但成药性不及水提醇沉部位。2种提取物制成软膏剂进行上述模型实验表明,与模型组比较,瑞香软膏能显著抑制角叉菜胶致大鼠炎性足肿胀的肿胀度,实验动物血清学分析白细胞介素-1β等炎症因子水平以及组织病理切片观察结果验证了该膏剂的抗炎作用。

结论:

本研究筛选出瑞香狼毒抗炎消肿有效部位为提取物A及提取物B,且2种提取物混合制作的瑞香软膏具有较强的炎症抑制作用。

瑞香狼毒  /  抗炎消肿  /  有效部位筛选
Objective:

To screen the anti-inflammatory and anti-swelling active fraction of Stellera chamaejasme Daphne odora, and to preliminarily explore its pharmacodynamics and mechanism of action.

Methods:

The toe swelling model was established in SD rats. The toe swelling, serum inflammatory factors and superoxide dismutase (SOD) activity were detected by daubing different extracts of Daphne odora chamaejasme and its ointment.

Results:

The water extract and ethanol precipitation of the drug had better anti-inflammatory and detumescence effect. The content was objective and the extraction process was simple. The 80% ethanol extract showed good anti-inflammatory and detumescence activity, but the drug activity was not as good as the former extract. Two types of extracts were formulated into an ointment for the aforementioned model experiments. The results indicated that, compared to the model group, the ointment significantly inhibited the swelling degree of inflammatory paw edema induced by carrageenan in rats. The serum samples of the experimental animals were analyzed for IL-1β and other inflammatory factors. Compared with the model group, the anti-inflammatory effect of the ointment was supported by IL-1β levels and the observations from tissue pathology sections. The activity of SOD was increased.

Conclusion:

Extract A and extract B are the effective parts of anti-inflammation and anti-swelling of Stellera chamaejasme Daphne odora.

Stellera chamaejasme Daphne odora  /  anti-inflammatory and swelling  /  extract
乌日尼乐, 吉木斯, 那生桑. 瑞香狼毒抗炎消肿有效部位及其作用机制研究. 中国新药杂志, 2025 , 34 (17) : 1858 -1864 . DOI: 10.20251/j.cnki.1003-3734.2025.17.011
WURINILE, JIMUSI, NASHENGSANG. Anti-inflammatory and anti-swelling active fraction of Stellera chamaejasme Daphne odora and its mechanism of action[J]. Chinese Journal of New Drugs, 2025 , 34 (17) : 1858 -1864 . DOI: 10.20251/j.cnki.1003-3734.2025.17.011
瑞香狼毒为瑞香科狼毒属植物瑞香狼毒(Stellera chamejasme L.)的干燥根,是常用蒙药材。瑞香狼毒在内蒙古自治区资源丰富,生长多集中于草原荒漠地区。味苦、辛,性涩、平[1],全株有毒,根具有潜在药用价值。蒙医用药历史悠久,在传统治疗中常用于杀“粘”、消肿、止疼,外用疗效可靠,是常用制剂哈布得仁-9味的君药而广泛应用于临床[2],对腮腺炎的疗效稳定可靠[3]。我国从瑞香狼毒中分离得到第一个单体化合物,即化学家黄文魁命名的狼毒素。1947年,苏联学者从瑞香狼毒中分离鉴定出4种呋喃型香豆素。其后,苏联、蒙古、日本等国家的学者也加入了研究行列。目前,对瑞香狼毒化学成分研究日趋深入,在其中发现了大量活性成分和许多有药用、农用价值的化合物,并开展了一系列药用评价研究,为促进瑞香狼毒的合理利用开发了研究线索。瑞香狼毒的化学成分较为复杂,目前研究发现主要包括香豆素类、黄酮类、木脂素类和萜类等多种活性成分[4-5]。瑞香狼毒抗肿瘤作用较显著,其作用机制包括调节肿瘤细胞周期、抑制肿瘤细胞增殖等方面。
本研究旨在采用经典的急性炎症模型探究蒙药瑞香狼毒不同提取物的抗炎消肿药效,筛选抗炎消肿有效部位,并进一步探究抗炎消肿作用机制,为其抗炎消肿物质探索奠定研究基础。
瑞香狼毒药材采自内蒙古自治区锡林郭勒盟正镶白旗,经内蒙古药品检验研究院塔娜主任药师鉴定为瑞香科植物瑞香狼毒的干燥根;地塞米松软膏(华润三九医药股份有限公司,批号:2204034X,规格:10 g,含量:0.75 mg·g-1);角叉菜胶(上海阿拉丁生化股份有限公司,批号:C121014-25G,规格: 50 g,纯度:99%);卡波姆(陕西正一药用辅料有限公司,批号:20220427,规格:1 kg);甘油(批号:20220127)、三乙醇胺(批号:20220125)、羟苯乙酯(批号:20220112)、聚山梨酯(批号:20211221)均购自江西益普生药业有限公司;肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)试剂盒(批号:20230610)、白细胞介素-1β(interleukin-1 beta,IL-1β)试剂盒(批号:20230412)、超氧化物歧化酶(superoxide dismutase,SOD)活性试剂盒(批号:20230508)、前列腺素E2(prostaglandin E2,PGE-2)试剂盒(批号:20230623)均购自基因美生物科技公司。
FA2004NO型十万分之一电子分析天秤(奥普实验设备有限公司);JP—100S型超声波清洗机(索尼克超声科技有限公司);MNT919310型游标卡尺(成都川牌机电有限公司);180—350G型大鼠固定器(北京环球生物科技有限公司)。
雄性SD大鼠,体质量(230±20) g,购自北京斯贝福生物技术有限公司,实验动物生产许可证号:SCXK(京)2019-0010,内蒙古医科大学实验动物使用许可证号:SYXK(蒙)2015-0001。同性别5只大鼠同笼饲养,适应观察3 d,饲料喂养,自由进食和饮水。研究经本单位实验动物医学伦理委员会批准,伦理批号:YKD202404057。
本研究所用瑞香狼毒药材均为本课题组分3次自采集的天然药材。
将瑞香狼毒饮片粉碎成粗粉,加入10倍量的水(浸没药材),浸泡30 min,大火煮开后文火微沸1 h,过滤,滤液备用;滤渣再加8倍量纯水微沸30 min,过滤后合并滤液,浓缩至刚挂瓶壁为止,放凉,加入乙醇约七成量,静止过夜,取滤液浓缩蒸干,得深黄色至棕色膏状物,不透明,有香气。收膏率约为18.54%。
取提取过提取物A的药渣,晒干,按料液比1∶30,加80%的乙醇超声提取60 min[6-7],共提2次,合并提取液,回收乙醇,蒸干,得深棕色膏状物,不透明,无特殊气味。收膏率约为6.4%。
取提取过提取物A的药渣,晒干,加入10倍量甲醇回流提取4 h,共提取3次,合并甲醇溶液,回收甲醇(至无醇味),加3倍量乙酸乙酯和3倍量纯水充分搅拌,静置,待溶液完全分层,取乙酸乙酯部位,减压浓缩蒸干,得深棕色膏状物,不透明,无特殊气味。收膏率约为3.29%。
将瑞香狼毒饮片粉碎成粗粉,加10倍量95%乙醇回流提取2 h,过滤。共提3次,合并滤液,回收乙醇(至无醇味),加3倍量石油醚和3倍量水充分搅拌[8],静置,待溶液完全分层后取石油醚部位,减压浓缩蒸干,得深棕色油状物,半透明,无特殊气味。收膏率约为0.53%。
蒙医在临床应用中将消肿九味散以蛋清等调和,外用涂抹治疗腮腺炎等各种炎性肿胀。由于瑞香狼毒是消肿九味散的君药,由此可推测瑞香狼毒水溶性部位及脂溶性部位均可通过蛋清发挥药效。为证明筛选出的2种提取物具有抗炎消肿作用,将其混合制成软膏,拟进行外部感染和肿痛治疗。
应选用性质稳定、具有适宜黏度、遇水易溶散、对皮肤无刺激性的基质,对含有的药物溶解性良好,不产生化学反应,不阻碍药物吸收。
取卡波姆适量,加蒸馏水使其充分溶胀,加入甘油搅拌;取三乙醇胺,于70 ℃水浴缓慢滴加并搅拌,使成透明凝胶基质,备用。另取提取物A和提取物B、羟苯乙酯、聚山梨酯置适宜容器中,加纯水适量,混合放置30 min,50~60 ℃水浴加热并不断搅拌使溶解,完全溶解后与凝胶基质混合,沿同一方向长时间搅拌,直至形成晶莹、细腻均匀的凝胶,加纯水至全量,搅匀。
1 g消肿九味散加蛋清制成外用涂抹搅和剂,皮肤涂抹约5 cm2,大鼠足趾约1 cm2,消肿九味散搅和剂涂抹用量为0.2 g。消肿九味散中瑞香狼毒比例为1/10,计算得大鼠足趾可用瑞香狼毒0.02 g·次-1。因瑞香狼毒提取物A、提取物B、提取物C及提取物D的提取率分别为18.54%,6.4%,3.29%以及0.53%,计算出0.02 g瑞香狼毒中提取物A、提取物B、提取物C及提取物D的含量分别为0.003 7,0.001 3,0.001 1,0.000 1 g。
瑞香狼毒提取物皮肤刺激实验:大鼠背部剃毛,涂抹10倍量或20倍量瑞香狼毒提取物观察48 h,均无红斑或水肿。通过预实验将4组瑞香狼毒有效部位粗提物10倍量以及20倍量分别给予SD大鼠,最终确定提取物A的给药量为20倍(0.074 g)、提取物B的给药量为10倍(0.013 g)、提取物C的给药量为20倍(0.021 g)、提取物D的给药量为10倍(0.001 g)。
瑞香软膏剂量的设定:每只大鼠足趾为1 cm2,空白基质涂抹量为1 mL。设定1 mL基质内包含0.074 g瑞香狼毒提取物A、0.013 g瑞香狼毒提取物B为高剂量,1 mL基质内包含0.037 g瑞香狼毒提取物A、0.006 5 g瑞香狼毒提取物B为低剂量。
取SD大鼠80只,采取随机数字表法分8组:模型组、空白组、阳性对照组、阴性对照组和提取物A,B,C,D处理组,每组10只。各处理组分别给予4种提取物,在大鼠同侧后足跖调敷。每次涂药后包扎,即固定保持6 h,解除时清洗用药部位;模型组不给药,阴性对照组给予蛋清,阳性对照组给予地塞米松软膏,固定6 h,持续给药7 d;空白组不做处理。模型组、阳性对照组、阴性对照组、各处理组末次给药结束1 h后,在给药足跖中心部位注射1%角叉菜胶0.1 mL·跖-1[9-10],之后分别在0.5,1,2,4,6,10 h用游标卡尺测量足趾肿胀宽度与厚度[11]。模型组大鼠足趾与空白组大鼠足趾比较,肿胀差异非常显著。
取SD大鼠48只,采用随机数字表法分6组:空白组、阳性对照组、模型组、阴性组、瑞香软膏高剂量组及低剂量组,每组8只。阳性对照组给予地塞米松软膏,阴性组给予空白基质1 mg·跖-1,高、低剂量处理组分别给予高剂量瑞香软膏和低剂量瑞香软膏1 mg·跖-1,持续给药7 d;空白组不做处理。模型组、阴性组、阳性对照组、各处理组末次给药结束1 h后,在给药足跖中心部位注射1%角叉菜胶0.1 mL·跖-1,测定0.5,1,2,4,6 h大鼠足跖的肿胀度变化。取肿胀足趾与未肿胀足趾,称重,做足容积分析(肿胀足趾-未肿胀足趾)。末次测定时静脉取血,血清分析炎症因子水平及SOD活性。切取足趾,以10%福尔马林溶液进行固定,石蜡包埋,苏木精-伊红染色,做病理组织学检查,观察组织病理学变化。
实验数据均以表示,用ANOVA进行统计学检验,组间比较以P<0.05为差异有统计学意义。
与空白组比较,模型组大鼠足跖肿胀度增加,差异有统计学意义,说明造模成功(见表1)。与模型组比较,阴性对照组大鼠足跖肿胀度变化无统计学意义,说明蛋清无抑制肿胀作用。4种提取物对大鼠足趾肿胀模型均有不同程度的抑制肿胀作用,其中提取物B组肿胀曲线最高点与阳性对照组基本一致(见图1)。提取物B组与模型组比较,1,4,6,10 h时大鼠足跖肿胀度显著降低(P<0.05或P<0.01);与阳性对照组比较,提取物B组大鼠足肿胀度下降速率在厚度指标上更快。提取物A组肿胀曲线最高点与阳性对照组比较相差较大,提取物A组不及阳性对照组,但其肿胀度下降速率更快,优于阳性对照组;提取物A组与模型组比较,0.5,10 h时大鼠足跖肿胀度显著降低(P<0.05或P<0.01),且10 h时肿胀度仅次于提取物B组。提取物C组与模型组比较,6 h时大鼠足跖肿胀度显著降低(P<0.05)。提取物D组大鼠足肿胀度变化无统计学意义。
与空白组比较,模型组大鼠足跖肿胀度增加,差异有统计学意义,说明造模成功(见表2)。与模型组比较,阴性组大鼠足跖肿胀度变化无统计学意义,说明空白基质无抑制肿胀作用。低剂量组与模型组比较,0.5,1,2,4,6 h时大鼠足跖肿胀度显著降低(P<0.05或P<0.01);高剂量组与模型组比较,1,2,6 h时大鼠足跖肿胀度显著降低(P<0.05或P<0.01);高、低剂量组间无差异。由图2可知,空白组大鼠足趾未肿胀;模型组大鼠肿胀度上升速率最快,且下降速率最慢;阳性组大鼠肿胀最高点程度最低,其次为瑞香软膏低剂量组和高剂量组,2,4,6 h低剂量组大鼠足趾肿胀度均小于高剂量组。在足容积分析中,空白组大鼠足容积趋于0;与空白组比较,模型组大鼠足容积变化具有统计学意义。瑞香软膏处理组与模型组比较,足容积变化无统计学意义,但呈明显下降趋势。模型组大鼠足容积最大,其次为高剂量组、阴性组、低剂量组、阳性组、空白组。
由“2.1”项下结果可知,阴性组与模型组大鼠足跖肿胀度相当,证明基质均无抑制肿胀作用,因此在使用ELISA法测定时除去阴性组,只测定其他5组数据,即空白组、阳性组、模型组、低剂量组、高剂量组。各实验组与模型组比较,炎性因子指标水平均有不同程度的统计学差异。阳性组与模型组比较,IL-1β,TNF-α水平显著降低(P<0.05或P<0.01);瑞香软膏高剂量组与模型组比较,IL-1β,PEG-2,TNF-α水平显著降低(P<0.05或P<0.01);瑞香软膏低剂量组与模型组比较,SOD水平显著升高(P<0.01);瑞香软膏低剂量组与模型组比较,PGE-2水平显著降低(P<0.05),说明瑞香软膏具有较强的炎症抑制作用,见表3图3
足跖病理切片HE染色结果显示,模型组大鼠组织整体观察到异常结构,可见坏死滑膜细胞和大量炎症细胞浸润,见图4。阳性组大鼠组织整体结构基本正常,可见结构清晰完整的组织滑膜及排列较为规则的滑膜细胞,未见明显滑膜细胞脱落坏死,未见滑膜细胞增生,未见明显的炎症细胞浸润。高剂量组大鼠组织整体结构异常程度相比模型组轻,组织中可见清晰完整的滑膜结构及排列较规则的滑膜细胞,可见较多滑膜明显增生,可见明显的炎症细胞浸润。低剂量组大鼠组织整体结构异常程度较轻,次于高剂量组,组织可见清晰完整的滑膜结构及排列较为规则的滑膜细胞,可见少量的滑膜细胞增生,可见少量的炎症细胞浸润。
蒙医临床应用中将瑞香狼毒研为细粉,以蛋清调和,外用涂抹给药,用于治疗诸多炎性肿胀,疗效可靠[12-13]。推测瑞香狼毒水溶性部位及脂溶性部位均可通过蛋清调和发挥药效,因此本研究以此为依据,经水提醇沉、80%乙醇提取及不同溶剂萃取方法获得提取物A、提取物B、提取物C、提取物D,将上述4种提取物分别给予角叉菜胶致足肿胀大鼠模型。《蒙药学》(1972年10月第一版)中记载“瑞香狼毒研细,开水调敷于患处,消除诸多肿胀”,但无法确定具体给药剂量。在蒙医临床应用中,将瑞香狼毒作为君药的方剂,即消肿九味散,以蛋清为赋形剂涂抹于患处,广泛用于治疗腮腺炎、乳腺炎等,因此本研究将瑞香狼毒各提取物的给药剂量按消肿九味散换算后以足趾肿胀度为指标进行测量。1%角叉菜胶皮下注射造模,该模型为急性炎症模型,炎症肿胀程度符合临床病理学研究结果。炎性肿胀指标结果显示,与模型组比较,提取物A组(0.5 h)与提取物B组(1,4,6,10 h)大鼠足跖肿胀度变化有统计学意义。因此,瑞香狼毒提取物A和提取物B抗炎消肿作用较显著,可作为下一步研究开发的有效部位。
瑞香狼毒原生药材粉末入药可与蛋清调敷使用,但存在剂型落后、载药量低、药效慢、涂抹极为不便、患者顺应性较差等缺点,因此以卡波姆等作为基质,将有效部位成分制成简易软膏使用。抗炎消肿实验评价结果显示,模型组与空白组比较,大鼠足跖肿胀度差异有统计学意义,证明模型建立成功;低剂量组与模型组比较,0.5,2,4,6 h大鼠足趾肿胀度差异具有统计学意义;高剂量组与模型组比较,1,2,6 h大鼠足趾肿胀度差异具有统计学意义。足趾病理切片结果表明,瑞香软膏处理组可减少炎症细胞浸润,并降低血清中炎症因子的表达。大鼠足趾肿胀度、足容积分析、血清炎症因子浓度及足趾病理切片分析表明,本软膏具有良好的药理学作用。
综上所述,瑞香狼毒提取物对角叉菜胶致大鼠足肿胀模型具有拮抗和消肿作用,为蒙药瑞香狼毒的研究开发提供了有价值的依据,为开发特色蒙药奠定基础。但筛选出的有效部位及本制剂中目标物的含量较分散,对有效物质的定位不够确切,有待开展进一步研究补充。
  • 内蒙古医科大学一流学科基金资助项目(MYX2022-R16)
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2025年第34卷第17期
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doi: 10.20251/j.cnki.1003-3734.2025.17.011
  • 首发时间:2026-03-06
  • 出版时间:2025-09-15
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  • 录用日期:2025-01-14
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内蒙古医科大学一流学科基金资助项目(MYX2022-R16)
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    1内蒙古医科大学蒙医药学院,呼和浩特 010110
    2呼和浩特市蒙医中医医院,呼和浩特 010110
    3林西县医院,赤峰 024000

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*那生桑,男,教授,研究方向:蒙药学。E-mail:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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