中国临床药理学杂志

RIP3介导的程序性坏死促进DMED大鼠阴茎组织损伤及药物干预的研究

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牛立盼 ¹^,² , 杨培 ¹ , 朱兵兵 ¹^,² , 金秀芳 ¹^,² , 杨承霞 ¹^,² , 李凯鑫 ¹ , 夏玉为 ¹ , 刘凤霞 ¹^,²

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(7): 983-988

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (7) : 983 -988

RIP3介导的程序性坏死促进DMED大鼠阴茎组织损伤及药物干预的研究

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牛立盼¹^,², 杨培¹, 朱兵兵¹^,², 金秀芳¹^,², 杨承霞¹^,², 李凯鑫¹, 夏玉为¹, 刘凤霞¹^,²

作者信息

^1.新疆医科大学基础医学院人体解剖学教研室，新疆维吾尔自治区乌鲁木齐 830011

^2.新疆地方病分子生物学重点实验室，新疆维吾尔自治区乌鲁木齐 830011

通讯作者:

刘凤霞，教授，硕士生导师 MP: 13579844723 E-mail: liufengxia555@126.com

作者简介:

牛立盼（1995-），女，讲师，主要从事男性生殖疾病的基础研究

Research on RIP3-mediated necroptosis promotes penile tissue damage and pharmacological intervention in DMED rats

Li-pan NIU¹^,², Pei YANG¹, Bing-bing ZHU¹^,², Xiu-fang JIN¹^,², Cheng-xia YANG¹^,², Kai-xin LI¹, Yu-wei XIA¹, Feng-xia LIU¹^,²

Affiliations

^1.Department of Human Anatomy, College of Basic Medicine Science, Xinjiang Medical University, Urumqi 830011, Xinjiang Uygur Autonomous Region, China

^2.Xinjiang Key Laboratory of Molecular Biology of Endemic Diseases, Urumqi 830011, Xinjiang Uygur Autonomous Region, China

出版时间: 2025-04-17 doi: 10.13699/j.cnki.1001-6821.2025.07.016

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摘要

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目的

探究受体相互作用蛋白激酶3（RIP3）介导的程序性坏死通路在糖尿病性勃起功能障碍（DMED）大鼠阴茎组织损伤中的作用，以及GSK872和伊木萨克片的干预效果。

方法

选择正常性功能的雄性SD大鼠，连续2 d注射45 mg·kg^-1链脲佐菌素构建糖尿病大鼠，筛选出DMED大鼠，并随机分为模型组、实验组、伊木萨克组和联合组。正常组和模型组均腹腔注射等量0.9% NaCl并灌胃等量蒸馏水；实验组腹腔注射1 mg·kg^-1 GSK872并灌胃等量蒸馏水；伊木萨克组腹腔注射等量0.9% NaCl并灌胃250 mg·kg^-1伊木萨克；联合组腹腔注射1 mg·kg^-1 GSK872并灌胃250 mg·kg^-1伊木萨克。用免疫组化法和免疫荧光法检测大鼠阴茎组织中RIP3、混合谱系激酶结构域样蛋白（MLKL）和瞬时受体电位阳离子通道联合亚家族M成员7（TRPM7）的表达情况，用蛋白质印迹法检测大鼠阴茎组织中α-平滑肌肌动蛋白（α-SMA）和Ⅰ型胶原蛋白（Collagen Ⅰ）的表达水平。

结果

正常组、模型组、实验组、伊木萨克组和联合组阴茎组织中RIP3阳性面积比分别为（7.71±1.92）%、（35.72±2.73）%、（20.20±2.51）%、（19.94±2.66）%和（9.31±1.98）%，MLKL阳性面积比分别为（7.39±1.73）%、（26.48±1.74）%、（15.66±1.87）%、（15.88±1.59）%和（8.45±1.65）%，TRPM7阳性面积比分别为（6.43±2.10）%、（35.77±1.78）%、（23.76±1.79）%、（25.24±2.08）%和（9.39±1.72）%，α-SMA蛋白相对表达水平分别为1.53±0.13、0.39±0.08、0.88±0.14、0.86±0.12和1.52±0.12，Collagen Ⅰ蛋白相对表达水平分别为0.29±0.10、1.20±0.14、0.73±0.07、0.71±0.11和0.31±0.10。模型组的上述指标与正常组比较、实验组的上述指标与模型组比较、伊木萨克组的上述指标与模型组比较、联合组的上述指标与模型组比较，在统计学上差异均有统计学意义（均P<0.05）。

结论

RIP3/MLKL/TRPM7程序性坏死通路可能通过促进细胞死亡和纤维化参与调控DMED大鼠病程，而GSK872和伊木萨克片可以通过抑制该通路来改善大鼠阴茎损伤。

关键词

伊木萨克片 / GSK872 / 受体相互作用蛋白激酶3/混合谱系激酶结构域样蛋白/瞬时受体电位阳离子通道亚家族M成员7 / 程序性坏死 / 糖尿病性勃起功能障碍

Abstract

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Objective

To investigate the role of the receptor-interacting protein kinase 3 (RIP3)-mediated necroptosis pathway in penile tissue damage in diabetes mellitus-induced erectile dysfunction (DMED) rats and the effects of GSK872 and Yimusake intervention in DMED rats.

Methods

Male SD rats with normal sexual function were selected, and diabetic rats were constructed by 2 consecutive days injections of streptozotocin (45 mg·kg^-1), DMED rats were screened and randomly divided into model group, experimental group, Yimusake group and combined group. The normal and model groups were injected intraperitoneally with an equal amount of 0.9% NaCl and gavaged with an equal amount of distilled water; the experimental group was injected intraperitoneally with 1 mg·kg^-1 GSK872 and gavaged with an equal amount of distilled water; the Yimusake group was injected intraperitoneally with an equal amount of 0.9% NaCl and gavaged with 250 mg·kg^-1 Yimusake; the combined group was injected intraperitoneally with 1 mg·kg^-1 GSK872 and gavaged with 250 mg·kg^-1 Yimusake. The expression of RIP3, mixed lineage kinase domain like protein (MLKL) and transient receptor potential melastatin 7 (TRPM7) were detected by immunohistochemistry and immunofluorescence, α-smooth muscle actin (α-SMA) and Collagen Ⅰ were detected by Western blotting in rat penile tissues.

Results

The positive area ratios of RIP3 in the penile tissues of normal, model, experimental, Yimusake and combined groups were (7.71±1.92)%, (35.72±2.73)%, (20.20±2.51)%, (19.94±2.66)% and (9.31±1.98)%; MLKL positive area ratios were (7.39±1.73)%, (26.48±1.74)%, (15.66±1.87)%, (15.88±1.59)% and (8.45±1.65)%; TRPM7 positive area ratios were (6.43±2.10)%, (35.77±1.78)%, (23.76±1.79)%, (25.24±2.08)% and (9.39±1.72)%; α-SMA protein relative expression levels were 1.53±0.13, 0.39±0.08, 0.88±0.14, 0.86±0.12 and 1.52±0.12; Collagen Ⅰ protein relative expression levels were 0.29±0.10, 1.20±0.14, 0.73±0.07, 0.71±0.11 and 0.31±0.10. The differences between the above indices in the model group compared with the normal group, the above indices in the experimental group compared with the model group, the above indices in the Yimusake group compared with the model group and the above indices in the combined group compared with the model group were all statistically significant (all P<0.05).

Conclusion

RIP3/MLKL/TRPM7 necroptosis pathway may participate in regulating the progression of DMED rats by promoting cell death and fibrosis, while GSK872 and Yimusake may ameliorate penile injury in rats by inhibiting this pathway.

Key words

Yimusake tablet / GSK872 / receptor-interacting protein kinase 3/mixed lineage kinase domain like protein /transient receptor potential melastatin 7 / necroptosis / diabetes mellitus-induced erectile dysfunction

引用本文

牛立盼, 杨培, 朱兵兵, 金秀芳, 杨承霞, 李凯鑫, 夏玉为, 刘凤霞. RIP3介导的程序性坏死促进DMED大鼠阴茎组织损伤及药物干预的研究. 中国临床药理学杂志, 2025 , 41 (7) : 983 -988 . DOI: 10.13699/j.cnki.1001-6821.2025.07.016

Li-pan NIU, Pei YANG, Bing-bing ZHU, Xiu-fang JIN, Cheng-xia YANG, Kai-xin LI, Yu-wei XIA, Feng-xia LIU. Research on RIP3-mediated necroptosis promotes penile tissue damage and pharmacological intervention in DMED rats[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (7) : 983 -988 . DOI: 10.13699/j.cnki.1001-6821.2025.07.016

基金

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国家自然科学基金资助项目(81860781)
新疆维吾尔自治区自然科学基金资助项目(2021D01C280)

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2025年第41卷第7期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.07.016

接收时间：2024-10-23
首发时间：2026-08-04
出版时间：2025-04-17

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收稿日期：2024-10-23

基金

国家自然科学基金资助项目(81860781)

新疆维吾尔自治区自然科学基金资助项目(2021D01C280)

作者信息

^1.新疆医科大学基础医学院人体解剖学教研室，新疆维吾尔自治区乌鲁木齐 830011

^2.新疆地方病分子生物学重点实验室，新疆维吾尔自治区乌鲁木齐 830011

通讯作者:

刘凤霞，教授，硕士生导师 MP: 13579844723 E-mail: liufengxia555@126.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.07.016

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2种不同金属材料的力学参数

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