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目的观察降糖三黄片对糖尿病肾病大鼠肾组织Toll样受体4(TLR4)/核因子-κB(NF-κB)通路及单核细胞趋化蛋白~(-1)(MCP~(-1))表达的影响,探讨降糖三黄片对糖尿病肾病的保护作用及其机制。方法将80只SD大鼠随机分为正常组10只,模型组70只。模型组大鼠予腹腔内注射链脲佐菌素(STZ)复制模型,成模大鼠随机分为模型组,降糖三黄片低、中、高剂量组(675,1350,2700 mg·kg~(-1)·d~(-1)),厄贝沙坦组(13.5 mg·kg~(-1)·d~(-1)),正常组和模型组灌服等剂量蒸馏水。给药8周后腹主动脉采血测空腹血糖,收集24 h尿液测定尿蛋白,免疫组化法检测各组肾组织中MCP~(-1)蛋白的分布,Western blot法检测各组肾组织中TLR4、NF-κB(P-p65)蛋白的表达。结果与正常组比较,模型组的空腹血糖、24 h尿蛋白及肾组织TLR4、NF-κB(P-p65)、MCP~(-1)蛋白表达均显著升高,差异有统计学意义(P<0.01)。与模型组比较,降糖三黄片低、中、高剂量组空腹血糖均显著降低,差异有统计学意义(P<0.01)。与模型组比较,降糖三黄片低、中、高剂量组及厄贝沙坦组肾组织TLR4、NF-κB(P-p65)、MCP~(-1)蛋白表达显著降低、尿蛋白排出显著减少,差异均有统计学意义(P<0.05,P<0.01)。结论降糖三黄片通过抑制TLR4/NF-κB通路,下调MCP~(-1)的表达,起到减少尿蛋白排出,延缓DN进展的作用。
Objective To observe the effects of Jiangtang Sanhuang Tablet on the expressions of TLR4 / NF-κB pathway and monocyte chemoattractant protein-1 (MCP - 1) in diabetic nephropathy rats. )) Expression, to explore the protective effect of Jiangtang Sanhuang Tablet on diabetic nephropathy and its mechanism. Methods Eighty SD rats were randomly divided into normal group (n = 10) and model group (n = 70). Rats in the model group were intraperitoneally injected with streptozotocin (STZ) and the model rats were randomly divided into model group, low, middle and high dosage Jiangtang Sanhuang tablets (675,1350,2700 mg · kg ~ (-1) · d ~ (-1)) and irbesartan (13.5 mg · kg ~ (-1) · d ~ (-1)) respectively. The normal and model groups were given the same dose of distilled water. After 8 weeks of administration, fasting blood glucose was collected from the abdominal aorta and urinary protein was collected for 24 hours. Immunohistochemistry was used to detect the distribution of MCP -1 protein in each group. Western blot was used to detect the renal tissue In TLR4, NF-κB (P-p65) protein expression. Results Compared with the normal group, the fasting blood glucose, 24 h urinary protein and the expression of TLR4, NF-κB (P-p65) and MCP -1 protein in the model group were significantly increased, the difference was statistically significant (P <0.01). Compared with model group, fasting blood glucose in low, medium and high dose Jiangsan Sanhuang tablets group was significantly lower (P <0.01). Compared with the model group, the expression of TLR4, NF-κB (P-p65) and MCP-1 in the low, medium and high dose and low dose Irbesartan groups were significantly decreased and the urinary protein excretion was significantly decreased Reduce, the differences were statistically significant (P <0.05, P <0.01). Conclusion Jiangtang Sanhuang tablet can reduce the excretion of urinary protein and delay the progression of DN by inhibiting TLR4 / NF-κB pathway and down-regulating the expression of MCP-1.