1,25-(OH)_(2)D_(3)干预糖尿病大鼠模型对P38MAPK与TGF-β1的影响及肾保护作用研究  

The effects of 1,25-(OH)_(2)D_(3) intervention on p38MAPK and TGF-β1 and renal protection in diabetic rats

作　　者：仇菊萍[1] 刘学燕 QIU Juping;LIU Xueyan(Department of Endocrinology,Guyuan People′s Hospital of Ningxia,Guyuan 756000,China;Department of Pediatrics,The third People′s Hospital of Yinchuan,Yinchuan 750001,China)

机构地区：[1]宁夏固原市人民医院内分泌科,宁夏固原756000 [2]宁夏银川市第三人民医院儿科,宁夏银川750001

出　　处：《宁夏医学杂志》2021年第1期8-11,F0003,共5页Ningxia Medical Journal

摘　　要：目的研究1,25-二羟维生素D3[1,25-(OH)_(2)D_(3)]干预糖尿病大鼠模型对P38丝裂原活化蛋白激酶(P38MAPK)与转化生长因子β1(TGF-β1)的影响。方法选用雄性大鼠作为实验动物,采用随机数字表法将大鼠分为A、B、C 3组,每组各28只。A组给予常规饲料喂养,B、C组给予高脂高胆固醇饲料喂养6周,糖尿病大鼠模型建模成功后,A组继续常规饲料喂养,B、C组继续给予高脂高胆固醇喂养,同时B组给予1,25-(OH)_(2)D_(3)干预,共7次。处死大鼠,分别在喂养开始时(T1)、建模成功时(T2)及1,25-(OH)_(2)D_(3)干预完成后2周时(T3)取血,检测血肌酐(Scr)、尿肌酐(Ucr)、血尿素氮(BUN)和胱抑素C(Cys-C)肾功能指标水平,计算内生肌酐清除率(Ccr)。处死大鼠后取肾组织,采用免疫组化法和Western blot法检测P38MAPK与TGF-β1表达情况。分析P38MAPK与TGF-β1的关系。结果 3组大鼠T2和T3时Ccr、BUN及Cys-C水平比较有统计学意义(P<0.05),其中T2时B、C 2组Ccr、BUN及Cys-C水平显著高于A组(P<0.05),T3时B组Ccr、BUN及Cys-C显著低于C组(P<0.05)。3组大鼠肾组织P38MAPK与TGF-β1表达差异具有统计学意义(P<0.05)。3组大鼠肾组织P38MAPK与TGF-β1蛋白相对表达量差异有统计学意义(P<0.05),B组大鼠P38MAPK与TGF-β1显著低于C组(P<0.05)。3组大鼠肾组织P38MAPK与TGF-β1蛋白相对表达量呈显著正相关性(r=0.418,P<0.05)。结论 1,25-(OH)_(2)D_(3)干预能显著改善糖尿病大鼠肾功能,这可能与其抑制P38MAPK与TGF-β1表达有关。Objective To study the effects of 1,25-dihydroxyvitam in 1,25-(OH)_(2)D_(3) intervention P38 mitogen activated protein kinase(P38MAPK)and transforming growth factor-β1(TGF-β1)and renal protection in diabetic rats.Methods 84 male rats were included in this study and the rats were divided into A,B and C group by random number table method,28 rats in each group.The group A was fed with conventional diet,group B and C were fed with high-fat and cholesterol diet for 6 weeks.The group A continued to be fed with conventional diet after the model of diabetic rats was established successfully,the group B and group C fed with high fat and cholesterol,the group B was given 1,25-(OH)_(2)D_(3) intervention for 7 times.The rats were killed,the blood was taken from the vein at the beginning of feeding(T1),at the end of modeling(T2)and at the time of two weeks after intervention of 1,25-(OH)_(2)D_(3)(T3),respectively.The levels of serum creatinine(Scr),urinary creatinine(Ucr),blood urea nitrogen(BUN)and cystatin C(Cys-C)renal function indexes were measured,and the endogenous creatinine clearance rate(Ccr)was calculated.The renal tissue was removed and after the rats were killed.The expression of p38 MAPK and TGF-β1 were detected by immunohistochemistry and Western blot.The relationship between p38 MAPK and TGF-β1 were analyzed.Results There were significant differences in the levels of Ccr,BUN and Cys-C between the three groups at T2 and T3,The levels of Ccr,BUN and Cys-C in group B and C were significantly higher than those in group A(P<0.05).The Ccr,BUN and Cys-C at T3 in group B were significantly lower than those in group C(P<0.05).There were significant difference in the relative expression of p38MAPK and TGF-β1 protein between the three groups(P<0.05).There was significant difference in the relative expression of p38MAPK and TGF-β1 protein between the three groups(P<0.05).The P38MAPK and TGF-β1 in group B were significantly lower than those in group C(P<0.05).There was significant difference in p38MAPK and TGF-β1 e

关 键 词：糖尿病大鼠 1 25-二羟维生素D3 P38丝裂原活化蛋白激酶 转化生长因子Β1 

分 类 号：R285.3[医药卫生—中药学]