| 陈 红,公欣华,陈丽君,石 霞,朱俊东.二氢杨梅素激活AMPK通路预防糖尿病肾病的作用研究[J].,2017,17(34):6613-6619 |
| 二氢杨梅素激活AMPK通路预防糖尿病肾病的作用研究 |
| Dihydromyricetin Prevents against Diabetic Nephropathy through the Activation of AMPK Pathway |
| 投稿时间：2017-06-06 修订日期：2017-06-30 |
| DOI：10.13241/j.cnki.pmb.2017.34.003 |
| 中文关键词: 二氢杨梅素 激活腺苷酸活化蛋白激酶 糖尿病肾病 自噬 |
| 英文关键词: Dihydromyricetin(DHM) Adenosine Monophosphate Activated Protein Kinase (AMPK) Diabetic nephropathy(DN) Autophagy |
| 基金项目:国家自然科学基金面上项目（81372975） |
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| 中文摘要: |
| 摘要 目的：探讨二氢杨梅素(DHM)对糖尿病肾病(DN)的预防作用及其与激活腺苷酸活化蛋白激酶(AMPK)通路的关系。方法：选择40只SD雄性大鼠，采用腹腔注射链脲佐菌素(STZ)60 mg/kg的方法建立DN大鼠模型，并将其分为正常组(CON)、糖尿病肾病组(DN组)、实验组(DHM50 mg/kg、100 mg/kg)各10只。其中，实验组分别给予DHM(50 mg/kg、100 mg/kg)灌胃，DN组则给予蒸馏水灌胃，持续8周。采用HE和Masson染色法观察肾脏的病理形态，ELISA法检测大鼠肾脏组织中I型胶原(COL I)、IV型胶原(COL IV)、纤维连接蛋白(FN)的含量，Western blot法检测大鼠肾脏组织中AMPK、转化生长因子-β1(TGF-β1)、α-平滑肌动蛋白(a-SMA)、雷帕霉素哺乳靶蛋白(mTOR)、自噬相关微管相关蛋白1轻链3(LC3Ⅰ/LC3Ⅱ)、Beclin-1蛋白的表达。结果：HE染色显示与DN组相比，DHM组系膜基质增生减轻、系膜区变窄，肾小囊腔变宽以及囊壁黏粘减轻；Masson染色显示DHM组较DN组的肾间质蓝染程度变浅。ELISA结果显示DHM组COL I、COL IV、FN的含量较DN组明显降低(P<0.01)，且100 mg/kg DHM处理组COL I、COL IV、FN的含量明显低于50 mg/kg DHM处理组(P<0.05)。Western blot检测结果显示DHM组肾脏组织AMPK、P-AMPK/AMPK、LC3Ⅰ/LC3Ⅱ和Beclin-1蛋白表达量显著高于DN组，且100 mg/kg DHM处理组以上指标均显著高于低剂量组(P<0.01)；而DHM组肾脏组织TGF-β1、α-SMA和mTOR的蛋白表达较DN组明显降低(P<0.01)，且100 mg/kg DHM处理组TGF-β1、mTOR表达显著低于50 mg/kg DHM处理组(P<0.05)。结论：DHM可显著减少DN的肾小球细胞外基质沉积，改善肾小球硬化和减轻肾脏纤维化的功能，其作用机制可能是通过激活AMPK/mTOR通路，促进细胞自噬和抑制TGFβ-1、α-SMA的表达。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the preventive effect of dihydromyricetin (DHM) on diabetic nephropathy (DN) and its relationship with Adenosine Monophosphate Activated Protein Kinase (AMPK) pathway. Methods: Forty male Sprague-Dawley rats were employed in present study, and rats model of DN were established by intraperitoneal injection of streptozotocin (STZ)60 mg/kg Then, all rats were divided into normal group (CON), diabetic nephropathy group (DN group) and the experimental group. The experimental groups were treated with DHM (50 mg/kg or 100 mg/kg) by lavage administration for 8 weeks, while the DN group was given the equal distilled water. The pathological morphology of the kidney was observed by using H&E and Masson staining. The contents of type I collagen (COLI), type IV collagen (COL IV) and fibronectin (FN) in rat kidney were detected by ELISA. The protein levels of AMPK, transforming growth factor-β(TGF-β1), α-smooth actin (α-SMA)and rapamycin mammalian target protein (mTOR), autophagy-associated microtubule-associated protein 1 light chain 3 (LC3Ⅰ/LC3Ⅱ), and Beclin-1 in rat kidney were determined by Western Blotting analysis. Results: H&E staining showed less mesangial matrix proliferation, more narrow-mesangial, as well as wider renal capsule space and reduced capsule wall adhesion in the DHM group when compared with the DN group. Masson staining displayed that the DHM group had higher degree of renal interstitial blue shallow. The result of ELISA showed less expression level of COL I, COL IV and FN in the DHM group than DN group. (P<0.05). In addition, DHM also up-regulated the protein level of AMPK, P-AMPK/AMPK, LC3Ⅰ/LC3Ⅱand Beclin-1, and the 100 mg/kg group increased more than 50 mg/kg (P<0.01). However, DHM reduced the expression level of TGF-β1, α-SMA and mTOR in rat kidney (P<0.01), and more significant decline of TGF-β1 and mTOR was detected with the 100 mg/kg group (P<0.05). Conclusion: DHM can reduce glomerular extracellular matrix deposition after DN, improving glomerular sclerosis and reducing renal fibrosis. Its mechanism may be through activating AMPK/mTOR pathway, enhancing cell autophagy and inhibiting expression of TGFβ-1 and α-SMA. |
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