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| 黄芪甲苷联合骨髓间充质干细胞对糖尿病肾病大鼠的肾脏保护作用研究 |
| Renal Protective Effect of Astragaloside IV Combined with Bone Marrow Mesenchymal Stem Cells on STZ-induced Diabetic Rats |
| 投稿时间：2019-05-29 修订日期：2019-05-29 |
| DOI： |
| 中文关键词: 黄芪甲苷 骨髓间充质干细胞 糖尿病肾病 氧化应激 |
| 英文关键词: Astragaloside IV Bone marrow mesenchymal stem cells Diabetic nephrology Oxidative stress |
| 基金项目:上海市浦东新区科技发展基金项目(PKJ2015-Y10)；国家自然科学基金项目（面上项目，重点项目，重大项目）（81573738）；上海健康医学院师资人才百人库项目 |
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| 中文摘要: |
| 目的: 研究黄芪甲苷 ( Astragaloside IV, AS-IV）联合骨髓间充质干细胞（Bone marrow mesenchymal stem cells, BMSCs）对链脲佐菌素（Streptozocin, STZ）诱导的糖尿病肾病（Diabetic nephrology, DN）大鼠肾脏的保护作用。方法：8周龄正常雄性 SD（Sprague Dawley, SD）随机选取8只作为正常对照组，其余大鼠给予腹腔注射60 mg/kg剂量STZ建立糖尿病模型。造模成功的大鼠随机分为模型组、BMSCs组和BMSCs + AS-IV组，每组8只。BMSCs+AS-IV组给予AS-IV 10mg/kg口服灌胃治疗。BMSCs组与BMSCs+AS-IV组分别于第1、2、4周尾静脉注射BMSCs (4×10６/500μl)，共移植3次，正常对照组和模型组尾静脉注射相同剂量的无血清DMEM培养基。于第10周末收集大鼠24小时尿液，并留取肾脏组织，测定24 h尿白蛋白排泄，观察肾脏病理改变，并采用免疫组织化学方法检测肾组织中α-SMA、Desmin、Nephrin、NOX4的表达。结果：与模型组相比，BMSCs组与BMSCs+ AS-IV组大鼠的肾脏病理损伤明显改善，肾组织中NOX4，Desmin和α-SMA蛋白表达降低，Nephrin蛋白表达增加，24 h尿白蛋白排泄均明显减轻，且BMSCs联合AS-IV治疗组效果更显著（P＜0.05）。结论：AS-IV联合BMSCs治疗可缓解糖尿病肾病大鼠肾脏病理损伤，改善DN大鼠肾组织的氧化应激，改善肾脏足细胞转分化，从而减轻蛋白尿排泄，具有肾脏保护作用。 |
| 英文摘要: |
| Objective: To study the renal protective effect of Astragaloside IV (AS-IV) combined with bone marrow mesenchymal stem cells (BMSCs) on streptozotocin (STZ) induced type 1 diabetic rats. Methods: Eight male Sprague-Dawley (SD) rats aged 8 weeks were randomly selected as the normal control group, and the remaining rats were given intraperitoneal injection of STZ（60 mg/kg）to establish type 1 diabetes models. The diabetic rats were randomly divided into model group, BMSCs treatment group and BMSCs + AS-IV treatment group (n=8). BMSCs+ AS-IV group was given AS-IV 10mg/kg solution by oral gavage. BMSCs group and BMSCs+ AS-IV group were injected with BMSCs (4×106/500μl) by caudal vein at week 1, 2 and 4, respectively. The normal control group and model group were injected with the same dose of serum-free DMEM culture medium. At the end of the 10th week, the excretion of urine albumin and renal histopathology were examined. The expressions of α-SMA, Desmin, Nephrin and NOX4 in the renal tissues were detected by immunohistochemistry. Results: Compared with diabetes model group, the renal pathological injury was significantly improved, the expression of NOX4, α-SMA and Desmin in the renal tissue was decreased, the expression of Nephrin was increased, and the excretion of urinary protein was reduced in BMSCs treatment group and BMSCs + AS-IV treatment group, and the combination treatment group was more significant. Conclusions: Treatment of AS-IV combined with BMSCs can alleviate renal pathological injury in DN rats, improve oxidative stress and reduce proteinuria excretion, has a protective effect on the kidney of STZ-induced type 1 diabetic rats. |
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