首页|加味芪黄饮改善糖尿病肾病的PTEN/PI3K/Akt/mTOR通路机制研究

加味芪黄饮改善糖尿病肾病的PTEN/PI3K/Akt/mTOR通路机制研究

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目的:研究加味芪黄饮通过PTEN/磷脂酰肌醇 3 激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶标(mTOR)通路改善糖尿病肾病(DN)的作用机制。方法:Sprague-Dawle(SD)大鼠利用高脂饲料饲养联合腹腔注射链脲佐菌素(STZ)建立DN模型,采用完全随机法分为模型组、加味芪黄饮低剂量组、中剂量组、高剂量组及氯沙坦组。各 10 只。根据临床用量换算,设定加味芪黄饮低剂量组、中剂量组、高剂量组[生药含量:200、400、800 mg·kg-1·d-1],空白组及模型组予 0。9%氯化钠注射液灌胃。8 周后取材,检测DN大鼠 24 h尿蛋白、血肌酐(SCr)、血尿素氮水平(BUN),苏木精-伊红(HE)染色观察肾脏病理变化,免疫组化检测肾组织中PTEN、PI3K、Akt和mTOR等蛋白表达。结果:与空白组相比,模型组大鼠24 h 尿蛋白、SCr、BUN水平显著升高(P<0。0001);加味芪黄饮干预后肾功能指标相比于模型组有所降低(P<0。001),免疫组化结果提示:模型组PTEN表达降低,PI3K、Akt、mTOR表达升高(P<0。01);加味芪黄饮干预后,PTEN表达量上升,PI3K、Akt及mTOR表达量下降,相比模型组差异均具有统计学意义(P<0。05)。加味芪黄饮高剂量组与氯沙坦组疗效差异无统计学意义(P>0。05)。结论:加味芪黄饮可能通过PTEN/PI3K/Akt/mTOR通路延缓DN发展。
Study on the Mechanism of PTEN/PI3K/Akt/mTOR Pathway of Jiawei Qihuang Yin in Improving Diabetic Nephropathy
Objective To study the mechanism of Jiawei Qihuang Yin in improving diabetic nephropathy(DN)through PTEN/phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)/mechanistic target of rapamycin(mTOR)pathway.Methods Sprague Dawle(SD)rats were fed with high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish a DN model.The rats were divided by completely random method into model group,low-dose group,middle-dose group,high-dose group of Jiawei Qihuang Yin and losartan group.There were 10 rats in each group.According to the conversion of clinical dosage,the low-dose group,middle-dose group and high-dose group of Jiawei Qihuang Yin were set(crude drug content:200,400,800 mg·kg-1·d-1.And the blank group and model group were given 0.9%sodium chloride injection by gavage.After 8 weeks,the levels of 24-hour urine protein,serum creatinine(SCr),and blood urea nitrogen(BUN)were measured.The pathological changes of kidney were observed by Hematoxylin-eosin(HE)staining,and the protein expressions of PTEN,PI3K,Akt and mTOR in renal tissue were detected by immunohistochemistry.Results Compared with the blank group,the levels of 24 h urine protein,SCr and BUN in the model group were significantly increased(P<0.0001),and the renal function indexes in the model group were lower than those in the model group after intervention with Jiawei Qihuang Yin(P<0.001).Immunohistochemical results showed that the expression of PTEN in the model group decreased,while the expression of PI3K,Akt,and mTOR increased(P<0.01).After the intervention of Jiawei Qihuang Yin,the expression of PTEN was increased,while the expression of PI3K,Akt and mTOR decreased,with statistical significances(P<0.05).There was no significant difference between the high-dose group of Jiawei Qihuang Drink and the losartan group(P>0.05).Conclusion Jiawei Qihuang Yin may delay the development of DN through the PTEN/PI3K/Akt/mTOR pathway.

Diabetic nephropathyJiawei Qihuang YinnPTEN/PI3K/Akt/mTOR

吴立友、毛凯凤、谢丹丹、王玉洁、李季、黄浩东

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广州医科大学附属中医医院,广东 广州 510130

糖尿病肾病 加味芪黄饮 PTEN/PI3K/Akt/mTOR

广东省中医药局管理局科研项目广东省中医药局项目广州市中医药和中西医结合科技项目

20212168202100972021A011008

2024

深圳中西医结合杂志
深圳市中西医结合临床研究所

深圳中西医结合杂志

影响因子:0.692
ISSN:1007-0893
年,卷(期):2024.34(7)