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Outline
To investigate the role and mechanism of paeoniflorin （PF） in sepsis-associated acute kidney injury （SA-AKI） in mice.
Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS. Twenty-four male C57BL/6J mice （6~8 weeks old，weighing 20~25 g） were randomly divided into Control group，model group，PF group （intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration），and β-catenin specific agonist BML284 group （10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration）. The renal histopathological changes were observed by HE staining and Paller scoring. ELISA was used to determine the contents of serum creatinine （Scr），neutrophil gelatinase-associated lipocalin （NGAL） and lactate，and renal contents of hexokinase 2 （HK2），lactate dehydrogenase A （LDHA），IL-1β and IL-18. Western blotting was performed to detect the expression of total β-catenin，p-β-cateninY654，nucleus β-catenin and c-Myc.
Compared with the Control group，the LPS group showed obviously damaged renal tissue，higher Paller score （P<0.05），increased serum Scr and NGAL levels （P<0.05），elevated renal contents of aerobic glycolytic indexes such as HK2，LDHA and serum lactate，as well as contents of IL-1β and IL-18 （P<0.05），and enhanced expression of total β-catenin，p-β-cateninY654，nucleus β-catenin and c-Myc in the renal tissue （P<0.05）. PF treatment attenuated the renal tissue damage，decreased Paller score （P<0.05），reduced serum Scr and NGAL levels （P<0.05），HK2，LDHA and serum lactate levels，and contents of IL-1β and IL-18 in renal tissues （P<0.05），and down-regulated the renal expression of total β-catenin，p-β-cateninY654，nucleus β-catenin and c-Myc when compared with the levels in the model group （P<0.05）. While，addition of BML284 reversed above effects of PF treatment with significant differences （P<0.05）.
PF can alleviate SA-AKI，and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway，thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.
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| 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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