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目的探讨过表达细胞间黏附分子1(intercellular cell adhesion molecule-1,ICAM-1)的间充质干细胞对小鼠1型糖尿病性肾病(DN)的疗效。方法小鼠随机分为正常对照组(NC组)、DN组、C3治疗组、C3-MIG R1治疗组和C3-MIGR1-ICAM-1治疗组。链脲佐菌素(STZ)腹腔注射小鼠建立DN动物模型,Masson染色检测小鼠肾脏病理改变。分别经尾静脉按1×10~5/只输注小鼠MSC细胞系(C3H10T1/2)、转染空载体的小鼠MSC(C3H10T1/2-MIGR1/MSC)和过表达ICAM-1的小鼠MSC(C3H10T1/2-ICAM-1/MSC),Masson染色检测模型小鼠肾纤维化改变,荧光显微镜观察MSC向肾脏归巢情况。用实时荧光定量PCR(Q-PCR)检测相关信号分子转化生长因子β1(TGF-β1)、SMAD2、胶原蛋白1(collagen1)的表达。结果 Masson染色结果显示,C3-MIGR1-ICAM-1治疗组中纤维化成分较DN组显著减少,提示过表达ICAM-1的MSC可显著降低小鼠肾纤维化程度。MSC移植治疗后的第3天和第7天,冰冻切片结果均可见MSC归巢至肾脏,但归巢细胞数均无统计学意义。Q-PCR检测相关信号分子的表达,结果显示,与正常对照组相比,DN小鼠肾内胶原蛋白1、TGF-β1、SMAD2表达量均显著升高(P<0.01),而过表达ICAM-1-MSC组的胶原蛋白1、TGF-β1、SMAD2的表达均显著低于DN组(P<0.01)。结论过表达ICAM-1间充质干细胞对DN肾具有一定保护作用。
Objective To investigate the effect of mesenchymal stem cells (ICAM-1) over-expressing intercellular cell adhesion molecule-1 on type 1 diabetic nephropathy (DN) in mice. Methods The mice were randomly divided into normal control group (NC group), DN group, C3 treatment group, C3-MIG R1 treatment group and C3-MIGR1-ICAM-1 treatment group. The mice were injected intraperitoneally with streptozotocin (STZ) to establish the model of DN. Masson staining was used to detect the renal pathological changes in mice. The mouse MSC (C3H10T1 / 2-MIGR1 / MSCs) transfected with empty vector and 1 × 10 ~ 5 / mouse MSC (C3H10T1 / 2) Mouse model of C3N10T1 / 2-ICAM-1 / MSC and Masson staining were used to detect renal fibrosis. Homing of MSCs to kidneys was observed by fluorescence microscopy. The expression of TGF-β1, SMAD2 and collagen 1 were detected by real-time fluorescence quantitative PCR (Q-PCR). Results The result of Masson staining showed that the fibrosis component in C3-MIGR1-ICAM-1 treatment group was significantly lower than that in DN group, suggesting that ICAM-1-overexpressing MSC could significantly reduce the degree of renal fibrosis in mice. On the 3rd day and the 7th day after MSC transplantation, MSC homing to the kidney was seen in the results of frozen section, but the number of homing cells was not statistically significant. Compared with normal control group, the expression of renal collagen 1, TGF-β1 and SMAD2 in DN mice were significantly increased (P <0.01) by Q-PCR and the expression of ICAM The expression of collagen 1, TGF-β1 and SMAD2 in -1-MSC group was significantly lower than that in DN group (P <0.01). Conclusion Overexpression of ICAM-1 mesenchymal stem cells has a protective effect on DN.