| 引用本文:梁国强1，蒋春波1，王健生2.滋肾通关方对糖尿病大鼠肾损伤的改善作用及其机制[J].世界中医药,2024,(03):. |
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| 滋肾通关方对糖尿病大鼠肾损伤的改善作用及其机制 |
| Improvement and Mechanism of Zishen Tongguan Prescription on Renal Injury in Diabetic Rats |
| 投稿时间：2022-08-26 |
| DOI：10.3969/j.issn.1673-7202.2024.03.005 |
| 中文关键词: 滋肾通关方 TGF-β1/Smads通路 糖尿病 肾损伤 肾纤维化 大鼠 |
| English Keywords:Zishen Tongguan Prescription TGF-β1/Smads pathway Diabetes Renal injury Renal fibrosis Rats |
| 基金项目:国家自然科学基金面上项目（82374546）；江苏省卫生健康委员会医学科研项目（M2021094）；江苏省高层次卫生人才“六个一工程”拔尖人才科研项目（LGY2020046）；苏州第九批姑苏卫生重点人才项目（GSWS2022107） |
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| 中文摘要: |
| 目的：研究滋肾通关方对糖尿病大鼠肾损伤的改善作用及其机制。方法：将50只8周龄雄性SD大鼠随机分为5组（每组10只）：对照组、模型组和滋肾通关方低剂量（7.0 g生药/kg）、中剂量（14.0 g生药/kg）、高剂量（28.0 g生药/kg）组。除对照组外，其余组大鼠高脂高糖喂养4周联合腹腔注射链脲佐菌素（STZ，35 mg/kg）构建糖尿病肾损伤大鼠模型。造模成功后，各组分别连续4周灌胃给予相应药物或生理盐水，1次/d。给药前和给药后第1、2、3、4周检测空腹血糖（FBG）、血清尿素氮（BUN）、肌酐（Cr）、总胆固醇（TC）、三酰甘油（TG）含量，酶联免疫吸附试验（ELISA）测定血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）含量；苏木精-伊红（HE）染色法观察肾损伤情况，蛋白质印迹法检测肾组织转化生长因子-β1（TGF-β1）/Smads通路相关蛋白的表达。结果：与对照组比较，模型组的大鼠FBG和血清BUN、Cr、TC、TG、TNF-α、IL-6、IL-1β均显著升高（均P<0.05）；肾组织可见病理学损伤改变；TGF-β1、Smad3、α-平滑肌肌动蛋白（α-SMA）和波形蛋白（Vimentin）的表达明显上调，而Smad7的表达明显下调。滋肾通关方低、中、高剂量组治疗4周后糖尿病肾损伤大鼠FBG和血清BUN、Cr、TC、TG、TNF-α、IL-6、IL-1β含量均明显降低（均P<0.05），肾组织病理学损伤明显改善，TGF-β1、Smad3、α-SMA、Vimentin表达下调且Smad7表达上调，在不同剂量的滋肾通关方观察组中，其作用表现出一定的剂量依赖性。结论：肾通关方可通过抑制TGF-β1/Smads信号通路改善糖尿病大鼠肾纤维化损伤。 |
| English Summary: |
| To investigate the therapeutic effects and mechanisms of Zishen Tongguan Prescription on improving renal damage in diabetic rats.Methods:Fifty 8-week-old male SD rats were randomly divided into five groups(n=10)，i.e.，control group，model group，and Zishen Tongguan Prescription low-dose(7.0 g/kg for crude drug)，medium-dose(14.0 g/kg for crude drug)，and high-dose(28.0 g/kg for crude drug) groups.Except for the control group，the rats in the other groups were fed on a high-fat and high-sugar diet for 4 weeks and then injected intraperitoneally with streptozotocin(STZ，35 mg/kg) to induce diabetic nephropathy model.After successful modeling，the rats in each group were orally administered the corresponding drugs or normal saline for 4 weeks，once a day.Fasting blood glucose(FBG)，serum urea nitrogen(BUN)，creatinine(Cr)，total cholesterol(TC)，and triglycerides(TG) levels were measured before and 1，2，3，and 4 weeks after administration.Enzyme-linked immunosorbent assay(ELISA) was used to detect serum tumor necrosis factor-alpha(TNF-α)，interleukin-6(IL-6)，and interleukin-1β(IL-1β) levels.Kidney damage was observed using hematoxylin-eosin(HE) staining，and the expression of transforming growth factor-β1(TGF-β1)/Smads pathway-related proteins in kidney tissues was detected using Western blot.Results:Compared with the control group，the rats in the model group showed significantly elevated FBG，serum BUN，Cr，TC，TG，TNF-α，IL-6，and IL-1β levels(all P<0.05)，as well as pathological changes in kidney tissues.The expression of TGF-β1，Smad3，α-smooth muscle actin(α-SMA)，and Vimentin was significantly upregulated，while the expression of Smad7 was significantly downregulated.After 4 weeks of treatment with Zishen Tongguan Prescription at low，medium，and high doses，the levels of FBG，serum BUN，Cr，TC，TG，TNF-α，IL-6，and IL-1β in diabetic nephropathy rats were significantly decreased(all P<0.05)，and kidney tissue pathology was significantly improved.The expression of TGF-β1，Smad3，α-SMA，and Vimentin was downregulated，while the expression of Smad7 was upregulated.The effects of Zishen Tongguan Prescription in different dose groups showed a certain dose-dependent relationship.Conclusion:Zishen Tongguan Prescription can improve diabetic nephropathy by inhibiting the TGF-β1/Smads signaling pathway. |
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