摘要
目的研究蜂胶乙醇提取物(EECP)对1型糖尿病大鼠肾脏的保护作用及相关机制。方法雄性SD大鼠68只,按55 mg/kg腹腔一次性注射链脲佐菌素(STZ)诱导1型糖尿病大鼠模型,72 h后检测大鼠尾静脉空腹血糖,将>16.7 mmol/L作为糖尿病模型。模型诱导成功后,按随机数字表法将大鼠分成5组:模型组、EECP 50 mg/kg、100 mg/kg、200 mg/kg组及二甲双胍组,每组10只,另外10只大鼠作为正常组。EECP 50 mg/kg、100 mg/kg、200 mg/kg组给予相应剂量EECP灌胃治疗,二甲双胍组给予二甲双胍75 mg/kg灌胃,药物溶剂为双蒸水,正常组和模型组给予等剂量双蒸水,给药体积为10 mL/g。12周后,检测各组大鼠血糖、血肌酐(Scr)、血尿素氮(BUN),肾组织丙二醛(MDA)及超氧化物歧化酶(SOD)含量;HE染色观察大鼠肾脏病理改变,免疫组织化学染色检测大鼠肾脏NADPH氧化酶4(NOX4)表达,Western blot检测大鼠肾脏NOX4、p38丝裂原活化蛋白激酶(MAPK)及p-p38 MAPK表达。结果与正常组相比,模型组血糖、Scr、BUN、MDA含量及NOX4和p-p38 MAPK表达明显升高,SOD活性明显降低(P<0.05);与EECP 50 mg/kg组比较,EECP 100 mg/kg组、EECP 200 mg/kg组、二甲双胍组血糖、Scr、BUN、MDA含量及NOX4和pp38 MAPK表达明显降低,SOD活性明显增加(P<0.05);与EECP 100 mg/kg组和EECP 200 mg/kg组比较,二甲双胍组血糖、Scr、BUN、MDA含量及NOX4和p-p38 MAPK表达明显降低,SOD活性明显增加(P<0.05)。结论EECP可通过降低血糖、增强机体抗氧化能力改善1型糖尿病大鼠肾脏损伤,可能是通过抑制p38 MAPK/NOX4信号通路的方式实现的。
Objective To study the protective effect and its related mechanism of ethanol extract of Chinese propolis(EECP)on kidney of type 1 diabetic rats.Methods Sixty-eight male SD rats were injected intraperitoneally(IP)with streptozotocin(STZ)once at a dose of 55 mg/kg for type 1 diabetic rat model.After 72 hours,the tail vein blood glucose of rat was detected,and rats with blood glucose>16.7 mmol/L were used as diabetes models.After the model induction,the type 1 diabetic rats were divided into five groups according to random number table method:model group,50 mg/kg,100 mg/kg,200 mg/kg of EECP groups and metformin(75 mg/kg)group,10 rats for each group.Another 10 normal rats were taken as the normal group.After 12 weeks,blood glucose,creatinine(Scr),urea nitrogen(BUN),malondialdehyde(MDA)and superoxide dismutase(SOD)were measured in each group.HE staining was used to observe renal pathological changes.The protein expressions of NADPH oxidase 4(NOX4)and p-p38 MAPK were detected by immunohistochemistry and Western blot assay.Results Compared with the normal group,the blood glucose,Scr,BUN,MDA and the expressions of NOX4 and pp38 MAPK were increased significantly in the model group,while the SOD activity decreased significantly(P<0.05).Compared with the EECP 50 mg/kg group,the blood glucose,Scr,BUN,MDA,and expressions of NOX4 and p-p38 MAPK were significantly decreased in the EECP 100 mg/kg group,EECP 200 mg/kg group and the metformin group,and the SOD activity was significantly increased(P<0.05).Compared with the EECP 100 mg/kg group and the EECP 200 mg/kg group,the blood glucose,Scr,BUN,MDA and expressions of NOX4 and p-p38 MAPK were significantly reduced in the metformin group,and SOD activity was significantly increased(P<0.05).Conclusion EECP can improve the renal injury of diabetic rats by reducing blood glucose and enhancing antioxidative ability,and the mechanism may be realized by inhibiting p38 MAPK/NOX4 signal pathway.
作者
罗影
左中夫
张俏
薛坤
刘畅
闵连秋
LUO Ying;ZUO Zhong-fu;ZHANG Qiao;XUE Kun;LIU Chang;MIN Lian-qiu(Department of Neurology,the First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121001,China;Department of Anatomy,Jinzhou Medical University)
出处
《天津医药》
CAS
北大核心
2020年第11期1040-1044,I0002,共6页
Tianjin Medical Journal
基金
中国博士后科学基金(2017M612870)
辽宁省自然科学基金(201602340)。
