冬虫夏草对糖尿病肾病大鼠肾组织HIF-1α及VEGF表达的影响  

Effect of Cordyceps sinensis on expressions of HIF-1α and VEGF in the kidney of rats with diabetic nephropathy

作　　者：袁明霞[1] 唐荣[1] 周巧玲[1] 刘抗寒[1] 肖舟[1] Veeraragoo Pouranan 

机构地区：[1]中南大学湘雅医院肾内科,长沙410008

出　　处：《中南大学学报（医学版）》2013年第5期448-457,共10页Journal of Central South University ：Medical Science

摘　　要：目的:观察缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelialgrowth factor,VEGF)在大鼠糖尿病肾病(diabetic nephropathy,DN)肾组织中的表达及冬虫夏草(Cordyceps sinensis,CS)干预后对其的影响,探讨冬虫夏草的抗缺氧损伤的肾保护机制。方法:健康雄性Wistar大鼠通过一次性腹腔注射链脲佐菌素(60 mg/kg)制作成糖尿病模型,4周时测定24 h尿蛋白>30 mg/d为DN模型大鼠(n=30),随机分为糖尿病肾病组(DN组,n=15)和冬虫夏草组(CS组,n=15),另取15只正常大鼠作为对照组(NC,n=15)。CS组予CS提取原液5.0 g/(kg d)灌胃,NC和DN组均予以等量饮用水灌胃,分别于灌胃2,4,6周时随机处死三组大鼠各5只,检测24 h尿蛋白定量、尿β-N-乙酰氨基葡萄糖苷酶(β-N-acetyl glucosaminidase,NAG酶)、血清肌酐水平;HE及MASSON染色观察肾脏组织形态学变化;反转录PCR方法检测HIF-1α和VEGF mRNA表达;免疫组织化学方法检测肾组织中HIF-1α及VEGF蛋白的表达。结果:与NC组相比较,DN组肾小管空泡变性明显,肾小球系膜区基质增多,24 h尿蛋白排泄量、尿NAG酶、血肌酐显著升高,肾组织HIF-1α和VEGF mRNA及其蛋白表达均显著增加(均P<0.05),两者的表达均随着病程延长而逐渐增强,且两组HIF-1α与VEGF表达呈正相关(r=0.850,r=0.887,均P<0.05);与DN组相比较,CS组大鼠肾小管病变程度减轻,24 h尿蛋白排泄量、尿NAG酶、血肌酐降低,肾组织HIF-1α和VEGF mRNA及其蛋白表达均下调(均P<0.05),但仍明显高于NC组(P<0.05),但CS治疗第4周、第6周HIF-1α的mRNA及蛋白水平差异无统计学意义(P>0.05)。结论:DN病大鼠肾组织HIF-1α及VEGF表达上调,两者呈正相关,提示DN肾组织存在慢性缺氧。CS可通过下调DN肾组织HIF-1α及VEGF的表达起到抗慢性缺氧损伤的肾保护作用。Objective： To examine the expressions of hypoxia inducible factor-lα （HIF-lα） and vascular endothelial growth factor （VEGF） in the kidney of rats with diabetic nephropathy before and after the treatment of Cordyceps sinensis, and to explore the mechanism of Cordyceps sinensis against hypoxia.Methods： The diabetes model was produced by intraperitoneal injection of 60 mg/kg streptozotocin, then the rats whose 24 h urine protein level was above 30 mg/d were thought to have suffered diabetic nephropathy. Xhirty rats were randomly divided into a diabetic nephropathy group （DN group, n=l5） and a Cordyceps sinensis group （CS group, n=15）, and another 15 normal rats served as a normal control group （NC group, n=l5）. The CS group were intragastrically administered Cordyceps sinensis extract liquid [5.0 g/（kg-d）], the other groups were intragastricaUy administered drinking water of equal volume. Five rats in each group were killed after 2, 4, and 6 weeks, The 24 h urine protein excretion, urine ^-N-acetyl glucosaminidase （NAGase） and serum creatinine were measured; the renal pathological changes were evaluated by HE and Masson staining; the mRNA and protein expressions of HIF-lα and VEGF were dectected by reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry.

关 键 词：糖尿病肾病 缺氧诱导因子-lα 血管内皮生长因子 冬虫夏草 

分 类 号：R285.5[医药卫生—中药学]