摘要
目的 观察哺乳动物雷帕霉素靶蛋白(mTOR)通路阻断剂对糖尿病肾病(DN)大鼠CD4+CD25highTreg的影响,探讨调节性T细胞(Treg)在DN中的可能机制。 方法 以正常大鼠作为对照组(A组),DN大鼠随机分为模型组(B组)、FK506干预组(C组)及ku0063794干预组(D组)。第4,8周时分别检测肾脏病理、肾组织mTOR、Raptor蛋白水平、Rictor、血白细胞介素-17(IL-17)、转化生长因子-β1(TGF-β1)和CD4+CD25highTreg。 结果 (1)4,8周时,B组的mTOR,Raptor和Rictor水平较A组均明显升高(P<0.05);4周时,C组的mTOR下降,低于B组(P<0.05);8周时,C,D组均下降,低于B组(P<0.001);4,8周时,C,D组的Raptor均下降低于B组(P<0.05);4周时,C,D组的Rictor均低于B组(P<0.05),8周时进一步下降,与A组比较差别无统计学意义,C,D组间比较差别无统计学意义。(2)4,8周时,B组的CD4+CD25highTreg明显低于A组(P<0.05),C,D组4周后逐步回升,高于B组(P<0.05);8周时进一步升高,均高于4周时(P<0.05);C,D组间比较差别无统计学意义。(3)C,D组的病理评分较B组均降低(P<0.05),组间比较差别无统计学意义。(4)4,8周时,B组的血TGF-β1和IL-17均高于A组(P<0.05),C,D组下降(P<0.05);4,8周时C组的TGF-β1低于D组(P<0.05);(5)8周时,B组大鼠的Rictor与CD4+CD25highTreg呈负相关(P<0.05),与TGF-β1,IL-17及病理评分呈正相关(P<0.05);Raptor与病理评分呈正相关(P<0.05),与CD4+CD25highTreg,TGF-β1及IL-17均无相关性(P>0.05)。 结论 CD4+CD25highTreg可能受Rictor-mTOR通路调控,参与DN的发病。
Objective To observe the effect of mammalian target of rapamycin (mTOR)pathway blocker on CD4 + CD25 high Treg in diabetic nephropathy (DN) rats, and to explore the possible mechanism of Regulatory T cell (Treg)in DN. Methods DN rats were randomly divided into model group (group B), FK506 intervention group (group C), and ku0063794 intervention group (group D), with normal rats as Control (Group A). Renal pathology, mTOR, Raptor, Rictor of renal tissue, serum interleukin-17(IL-17), transforming growth factor-β1(TGF-β1 ), and blood CD4 + CD25 high Treg were detected at 4th and 8th weeks. Results (1) mTOR, Raptor and Rictor in group B were significantly higher than those in group A at the 4th and 8th weeks (P<0.05). The mTOR in group C decreased at 4th week, which was lower than that in the group B (P<0.05). mTOR in groups C and D were lower than that in group B at 8th week (P<0.001). The Raptor in groups C and D were lower than that in B group at 4th and 8th weeks (P<0.05). The Rictor of the two groups (C and D) was lower than that of B group at 4th week (P<0.05). After 8 weeks, there was no difference in Rictor between groups C and D.(2) CD4 + CD25 high Treg in group B was significantly lower than that in group A at 4th and 8th weeks(P<0.05). CD4 + CD25 high Treg in groups C and D gradually recovered after 4 weeks, higher than in group B ( P<0.05 );and it further increased at 8th week, higher than that at 4th week (P<0.05);There was no difference between groups C and D.(3) Pathological scores of the groups C and D were lower than that of group B (P<0.05). There was no difference between the groups C and D.(4) Serum TGF-β1 and IL-17 in group B were higher than those in group A at 4th and 8th weeks (P<0.05), and they decreased after intervention (P<0.05). TGF-β1 in group C was lower than that in group D at 4th and 8th weeks (P<0.05).(5) At 8th week, Rictor was negatively correlated with CD4 + CD25 high Treg (P<0.05), and positively correlated with TGF-β1, IL-17, and pathological scores (P<0.05). Raptor was positively correlated with pathological scores (P<0.05), and there was no correlation with CD4 +CD25 high Treg, TGF-β1,or IL-17 (P>0.05). Conclusion CD4 + CD25 high Treg may be regulated by the Rictor-mTOR pathway and participate in the pathogenesis of diabetic nephropathy.
作者
曾艳
赵青
周静
李秋月
ZENG Yan;ZHAO Qing;ZHOU Jing;LI Qiuyue(Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China)
出处
《福建医科大学学报》
2019年第3期152-157,共6页
Journal of Fujian Medical University
基金
江西省自然科学基金(20161BAB205233)
