黄芪加强代谢综合征大鼠肾脏血管紧张素转换酶2的表达

Radix Astragali Enhanced Angiotensin Converting Enzyme 2 Expression in Kidney in Rats with Metabolic Syndrome

    摘要
  • 摘要: 目的探讨代谢综合征(MS)大鼠肾脏血管紧张素转换酶2(ACE2)表达的变化及黄芪对其的影响。方法雄性Wistar大鼠60只随机分为6组,每组10只,分别为正常对照组、果糖诱导的MS模型组、MS+缬沙坦20mg/(kg·d)组(缬沙坦组)、MS+黄芪1.5g/(kg·d)组(低剂量组)、MS+黄芪3.0g/(kg·d)组(中剂量组)、MS+黄芪6.0g/(kg·d)组(高剂量组)。6周末,用实时定量RT-PCR和免疫组化法分别从基因和蛋白水平检测各组大鼠肾脏ACE2的表达,用放免法检测肾脏血管紧张素Ⅱ(AngⅡ)水平。结果各组肾功能指标肌酐、尿素氮之间无明显差异,肾脏HE染色结果示药物干预组肾小球基底膜和系膜区的形态改变较模型组明显减轻。缬沙坦组大鼠肾脏AngⅡ浓度较MS组增高缬沙坦组:(27.5±2.5)比MS组:(20.5±1.9)ng/g,P<0.01,黄芪能剂量相关地降低AngⅡ的水平黄芪低剂量组:(18.0±1.9),黄芪中剂量组:(16.0±1.9),黄芪高剂量组:(14.1±1.7)比MS组:(20.5±1.9)ng/L,P<0.05。与正常对照组相比,MS模型组大鼠ACEmRNA表达上升76%、ACE2mRNA表达下降58%(ACE:1.76±0.12比对照组:1.00±0.13;ACE2:0.42±0.07比对照组:1.00±0.07,P<0.01)。缬沙坦和黄芪能剂量相关地增加肾脏ACE2mRNA水平(缬沙坦组:0.7±0.08,黄芪低剂量组:0.57±0.09,黄芪中剂量组:0.67±0.08,黄芪高剂量组:0.84±0.1比MS组:0.42±0.07,P<0.01)和蛋白的表达(缬沙坦组:0.29±0.03,黄芪低剂量组:0.22±0.03,黄芪中剂量组:0.27±0.02,黄芪高剂量组:0.38±0.04比MS组:0.18±0.02,P<0.05),降低ACEmRNA的表达(P<0.01)。结论MS大鼠肾脏形态有改变,局部ACE2表达水平降低,黄芪可以延缓MS大鼠肾脏病变,提高肾脏ACE2的表达。

     

    Abstract: Objective Angiotensin-converting-enzyme 2（ACE2） is an novel peptide in renin-angiotensin system（RAS） and has been emerged as a new target for treatment of hypertension and diabetes. We aimed to investigate the effect of Radix Astragali on the expression of angiotensin-converting enzyme 2 （ACE2） in kidney in rats with metabolic syndrome. Methods Sixty adult male Wistar rats were treated randomly as following approaches:normal control （n=10）,fructose-induced MS （n=10）,MS+valsartan 20 mg/（kg·d） （valsartan group,n=10）,MS+Radix Astragali 1.5 g/（kg·d） （low dose,n=10）,MS+Radix Astragali 3.0 g/（kg·d） （intermediate dose,n=10） and MS+Radix Astragali 6.0 g/（kg·d） （high dose,n=10） for 6 weeks. ACE and ACE2 mRNA in kidney were determined by real time RT-PCR and ACE2 protein was measured by immunohistochemistry. Angiotensin Ⅱ in kidney was measured with radioimmunoassay. Results There were no different on serum creatinine and urea among groups,but both valsartan and Radix Astragali significantly improved the morphological change of kidney in MS. Ang Ⅱ in kidney was increased in valsartan group compared with MS group valsartan group:（27.5±2.5） vs MS group:（20.5±1.9） ng/g,P＜0.01,while Radix Astragali dose dependently decreased Ang Ⅱ content in rats low dose group:（18.0±1.9）,intermediate dose group:（16.0±1.9）,high dose group:（14.1±1.7） vs MS group:（20.5±1.9）ng/g,P＜0.05. The expression of ACE mRNA in MS kidney were increased by 76% than that in the normal control group,ACE2 mRNA were decreased by 58% （1.76±0.12） vs MS group:（1.00±0.13）; （0.42±0.07） vs MS group:（1.00±0.07）ng/g,P＜0.01. Analogus to valsartan,Radix Astragali dose-dependently increased the ACE2 mRNA levels in kidney valsartan group:（0.70±0.08）,low dose group:（0.57±0.09）,intermediate dose group:（0.67±0.08）,high dose group:（0.84±0.10） vs MS group:（0.42±0.07）ng/g,all P＜0.01 and ACE2 protein expression （valsartan group:0.29±0.03,low dose group:0.22±0.03,intermediate dose group:0.27±0.02,high dose group:0.38±0.04 vs MS group:0.18±0.02,P＜0.05）,and concomitantly decreased the expression of ACE mRNA （all P＜0.05）. Conclusion ACE2 expression in kidney was decreased in rat with MS. Radix Astragali dose-dependently increase the expression of ACE2 in kidney.

     

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