摘要
目的 :观察四氧嘧啶诱发的糖尿病大鼠肾小球中蛋白激酶Cα(PKCα)、转化生长因子 - β1(TGF - β1)和α-平滑肌肌动蛋白 (α -SMA)表达的动态变化 ,探讨 3者之间相互关系以及与肾损害之间的关系。方法 :将大鼠随机分为正常对照组 (A组 ) ,糖尿病 1周组 (B组 ) ,糖尿病 1月组 (C组 )和糖尿病 2月组 (D组 )。用免疫组化和Western印迹法检查PKCα ,TGF - β1和α -SMA在肾小球的表达情况。光镜观察肾组织的形态改变 ,生化法测定大鼠血糖 ,血脂 ,血尿肌酐以及尿蛋白。结果 :糖尿病各组肾小球PKCα和TGF - β1的表达多于正常组 (P <0 0 5 ) ,糖尿病各组PKCα,TGF - β1和α -SMA 3者间呈正相关 ,并且与肾脏病变程度呈正相关。结论 :糖尿病早期肾组织PKCα表达持续增加 ,可使肾小球滤过率和滤过膜通透性增加 ,参与了肾病早期蛋白尿的发生机制 ,使TGF - β1增多并诱导α-SMA的表达 ,标志着肾脏固有细胞激活及表型转变和肾脏组织学改变。
AIM: To observe the dynamic changes of expression of PKCα , TGF-β 1 and α-SMA in glomeruli of diabetic rats induced by the alloxon and to invesitigate their roles in the diabetic nephropathy(DN). METHODS: Rats were randomly divided into four groups: normal control group (group A), diabetic group of one week (group B), diabetic group of one month (group C), diabetic group of two months (group D). Immunohistochemistry and Western blotting were used to detect the expression of PKCα, TGF-β 1 and α-SMA in renal tissue of all groups. Blood glucose, triglycerides, cholesterol, creatinine and urine protein were analysed by chemical methods. The morphological changes of renal tissue were checked through microscopy. RESULTS: The expression of PKCα and TGF-β 1 in renal tissue of diabetic groups were increased comparing with those of nomal control group( P <0.05). The mesangial cells expressed α-SMA in two months group. Chronologically the expression of PKCα, TGF-β 1 and α-SMA were positively correlative with each other and the impairment of kidney was also observed. CONCLUSIONS: During the DN process the expression of PKCα increased. PKCα raised GFR and the permeability of glomerular filtration membrane which enhanced urinary albumin excretion. PKCα also increased expression of TGF-β and therefore to induce the expression of α-SMA. The appearance of α-SMA was a marker of the phenotypic transform of renal cells.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2003年第9期1238-1241,T006,共5页
Chinese Journal of Pathophysiology
基金
贵州省自然科学基金资助项目 (No .D2 0 0 0- 8)
关键词
蛋白激酶C
转化生长因子-Β
平滑肌肌动蛋白
肾小球
糖尿病
大鼠
Protein kinase C
Transforming growth factor beta
Smooth muscle actin
Glomerulus
Diabetes mellitus
Rats