刘玲伶,严瑞,王圆圆,石明隽,郭兵
LIU Lingling,YAN Rui,WANG Yuanyuan,SHI Mingjun,GUO Bing

• 1:贵州医科大学病理生理学教研室
• 2:贵州医科大学重大疾病发病机制及药物防治特色重点实验室
• 3:贵州医科大学附院肾内科

摘要(Abstract)：

目的:探讨糖尿病(DM)小鼠肾组织中过氧化物酶增殖物激活受体γ(PPARγ)和第10号染色体缺失的磷酸酶和张力蛋白同源基因(PTEN)在肾纤维化过程中的表达变化及可能机制。方法:用链脲佐菌素(STZ)复制DM小鼠模型,并设正常对照组(NC组),每组8只,饲养16周后处死小鼠取肾组织,采用HE和Masson染色观察肾组织形态变化,SP法检测肾组织中E钙黏蛋白(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)的表达,Western blot检测肾组织中PPARγ、PTEN、蛋白激酶B1(protein kinase B1,PKB1/Akt1)、磷酸化蛋白激酶B1[p-Akt1(Ser~(450))]蛋白的表达,qRT-PCR检测肾组织中PPARγ和PTEN mRNA的变化。结果:与NC组比较,DM组小鼠E-cadherin表达减少,α-SMA表达增多;DM组肾组织p-Akt1(Ser~(450))蛋白表达增加,PPARγ、PTEN蛋白及mRNA表达减少,差异有统计学意义(P<0.05)。结论:PPARγ可能通过调节PTEN转录水平减少PTEN的表达,从而促进DM肾脏纤维化病变的发生
Objective: To investigate the expression change of peroxisome proliferator-activated receptor( PPAR),phosphatase and tensin homolog deleted on chromosome ten( PTEN) during the renal fibrosis process of diabetic mice and its possible mechanism. Methods: The diabetic mice were established by tail-vein injection of streptozotocin,and the other group was normal control( NC) group. After16 weeks,the mice were sacrificed and the pathological change of kidney were observed with HE and Masson staining. Meanwhile,immunohistochemistry were employed to detect the protein expression of E-cadherin and α-smooth muscle actin( α-SMA) in the renal tissue,and Western blot was applied to examine the protein levels of PPARγ,PTEN,Akt1 and p-Akt1( Ser450). In addition,the expression of PPARγ and PTEN mRNA were detected by qRT-PCR. Results: Compared with NC group,E-cadherin expression decreased and α-SMA levels increased in DM group( P < 0. 05),the expression of p-Akt1( Ser~(450)) protein increased in DM group( P < 0. 05),while the protein level of PPARγ and PTEN decreased( P < 0. 05). Moreover,the levels of PPARγ and PTEN mRNA markedly decreased in DM group( P < 0. 05). Conclusion: PPARγ may down-regulate the expression of PTEN by restraining the translational level of PTEN,thus aggravating fibrosis.

关键词(KeyWords)： 糖尿病肾病;蛋白激酶类;PPARγ蛋白;PTEN蛋白;p-Akt1(Ser450)蛋白
diabetic nephropathy;protein kinases;PPARγ protein;PTEN protein;p-Akt1(Ser450) protein

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81360116);; 贵州省科技厅社发攻关项目[黔科合SY字(2014)3021号];贵州省科技厅联合基金项目[黔科合LH字(2014)7124号];; 贵州省卫计委科技基金项目(gzwjkj2014-1-007)

作者(Author): 刘玲伶,严瑞,王圆圆,石明隽,郭兵
LIU Lingling,YAN Rui,WANG Yuanyuan,SHI Mingjun,GUO Bing

DOI: 10.19367/j.cnki.1000-2707.2017.04.007

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