| 摘要: |
| 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）60 mg/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、3.0 g/kg津力达颗粒），津力达+通心络组（1.5 g/kg津力达颗粒+0.4 g/kg通心络超微粉），二甲双胍组（50 mg/kg二甲双胍）和沙格列汀组（1 mg/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。 |
| 关键词: 津力达颗粒 1型糖尿病 生长激素 胰岛素样生长因子1 肾 |
| DOI：10.16781/j.0258-879x.2016.08.1028 |
| 投稿时间：2015-12-15修订日期：2016-03-08 |
| 基金项目:国家重点基础研究发展计划（“973”计划，2005CB523304）. |
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| The protective effect of Jinlida granules on kidney of type 1 diabetic rats |
| LU Xiao-xiao,WANG Chao-qun,LIU Zi-yu,ZOU Jun-jie,LIU Zhi-min* |
(Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author) |
| Abstract: |
| Objective To explore the protective effect of Jinlida granules on kidney tissues of type 1 diabetic rats, and to elucidate the related mechanism. Methods SD rats were intraperitoneally injected with streptozotocin (STZ, 60 mg/kg) to establish type 1 diabetic models. Then the model rats were randomly divided into diabetic model group, low-, medium- and high-dose Jinlida groups (0.75, 1.5 and 3.0 g/kg Jinlida granules, respectively), Jinlida+Tongxinluo (TXL) group (1.5 g/kg Jinlida granules+0.4 g/kg TXL), metformin group (50 mg/kg metformin), and saxagliptin group (1 mg/kg saxagliptin), with each group containing 5 rats. Five healthy rats served as normal controls. Eight weeks after administration of drugs or placebo, the levels of growth hormone (GH), growth hormone receptor (GHR), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF-1R), and insulin-like growth factor 1 binding protein 1(IGFBP-1) mRNA were detected by real-time quantitative PCR, the expressions of MAPK pathway related proteins and fibronectin (FN) were determined by Western blotting; and H-E staining, Masson staining and PAS staining were used to observe the morphological changes of kidney tissues. Results Compared with the normal control group, the levels of GH, GHR, IGF-1, IGF-1R mRNA and the protein expressions of p-ERK, p-JNK, and FN of kidney tissues were significantly increased (P<0.01), with cellular proliferation and fibrous deposition seen in the kidney tissues in the diabetic model group. After intervention with middle- and high-dose Jinlida granules, the levels of GH, GHR, IGF-1, and IGF-1R mRNA and ratios of p-ERK/ERK, p-JNK/JNK, and FN protein expression were significantly decreased (P<0.05, P<0.01), with alleviated kidney tissues fibrosis. Conclusion Jinlida granules can protect kidney tissues of type 1 diabetic rats, which is probably through up-regulating the levels of GH and IGF-1 mRNA and inhibiting the activation of the MAPK pathway. |
| Key words: Jinlida granules type 1 diabetes mellitus growth hormone insulin-like growth factor 1 kidney |
