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目的探讨津力达颗粒对1型糖尿病大鼠肾脏的保护作用及作用机制。方法 SD大鼠腹腔注射链脲佐菌素(STZ)60mg/kg制备1型糖尿病模型。将造模成功的糖尿病SD大鼠随机分为糖尿病模型组,低、中、高剂量津力达组(0.75、1.5、3.0g/kg津力达颗粒),津力达+通心络组(1.5g/kg津力达颗粒+0.4g/kg通心络超微粉),二甲双胍组(50mg/kg二甲双胍)和沙格列汀组(1mg/kg沙格列汀),每组5只;另取5只未造模大鼠作为正常对照组。各组大鼠予以药物或安慰剂灌胃,8周后实时定量PCR检测大鼠肾脏组织生长激素(GH)及其受体(GHR)、胰岛素样生长因子1(IGF-1)及其受体(IGF-1R)、胰岛素样生长因子结合蛋白1(IGFBP-1)mRNA的表达情况,蛋白质印迹法检测丝裂原活化蛋白激酶(MAPK)通路相关蛋白及纤维连接蛋白(FN)的表达水平,H-E染色、Masson染色和PAS染色观察肾脏组织形态学变化。结果同正常对照组相比,糖尿病模型组大鼠肾脏组织GH、GHR、IGF-1、IGF-1R mRNA表达水平增加(P<0.01),胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)磷酸化水平及FN蛋白表达水平升高(P<0.01),伴肾脏组织细胞增殖、纤维沉积;中、高剂量津力达干预后,大鼠肾脏组织GH、GHR、IGF-1、IGF-1R mRNA的表达水平降低(P<0.01),p-ERK/ERK、p-JNK/JNK的比值和FN蛋白的表达水平也降低(P<0.05,P<0.01),且肾脏组织纤维化程度明显改善。结论津力达颗粒对1型糖尿病大鼠肾脏有保护作用,其作用可能是通过降低大鼠肾脏GH、IGF-1的水平和抑制MAPK通路的激活来实现的。
Objective To investigate the protective effects of Jinlida Granules on the kidney of type 1 diabetic rats and its mechanism. Methods SD rats were intraperitoneally injected with streptozotocin (STZ) 60mg / kg to prepare type 1 diabetic model. Diabetic SD rats were randomly divided into diabetic model group, low, medium and high doses of Jin Lida group (0.75,1.5,3.0 g / kg Jin Lida particles), Jin Lida Tongxinluo group ( 1.5g / kg Jin Li Da particles + 0.4g / kg Tongxinluo superfine powder), metformin group (50mg / kg metformin) and saxagliptin group (lmg / kg saxagliptin) Five non-model rats served as normal control group. Rats in each group were given drugs or placebo. After 8 weeks, real-time quantitative PCR was used to detect the expression of growth hormone (GH), its receptor (GHR), insulin-like growth factor 1 (IGF-1) (IGFBP-1) and insulin-like growth factor-binding protein 1 (IGFBP-1) mRNA were detected by Western blotting. The expression of MAPK pathway-related protein and fibronectin (FN) The morphological changes of kidney were observed by HE staining, Masson staining and PAS staining. Results Compared with the normal control group, the expression of GH, GHR, IGF-1 and IGF-1R mRNA in diabetic rats increased (P <0.01), the expression of extracellular signal regulated kinase (ERK), c-Jun amino terminal The phosphorylation of JNK and the expression of FN protein increased (P <0.01), accompanied with the proliferation and deposition of renal cells. After intervention of middle and high dose of Jinlida, the levels of GH, GHR, IGF-1 (P <0.01). The ratio of p-ERK / ERK, p-JNK / JNK and the expression of FN protein also decreased (P <0.05, P <0.01) Significantly improved the degree of. Conclusion Jinlida Granules have a protective effect on the kidney of type 1 diabetic rats, and its effect may be through reducing the levels of GH and IGF-1 in the kidney and inhibiting the activation of MAPK pathway.