目的 探讨低聚原花青素(OPC)抑制TLR 4/NF-κB通路对糖尿病肾病(DKD)大鼠的肾保护和炎症因子抑制作用。方法 通过腹腔注射链脲佐菌素(50 mg/kg)、高脂高糖饮食制造DKD大鼠模型,后分别使用低、中、高剂量OPC(125、250和500 mg/kg)灌胃治疗DKD大鼠。8周后检测大鼠的血糖水平、肾脏指数、尿微量白蛋白定量、血尿素氮、血肌酐等肾损伤指标。采用ELISA试剂盒检测血清和肾皮质中IL-1β、IL-6和MCP-1等炎症因子的浓度。Western blot分析TLR 4/NF-κB相关蛋白的表达。结果 OPC低、中、高剂量组大鼠肾小球病理状态较模型组改善显著。与模型组相比,OPC中、高剂量组大鼠的空腹血糖、肾脏指数、尿微量白蛋白、血清肌酐和血尿素氮水平较模型组显著降低(P均<0.05),血清、肾脏中IL-1β、IL-6和MCP-1水平均较模型组显著降低(P均<0.05)。Western blot分析显示,与模型组相比,OPC中、高剂量组大鼠的TLR 4蛋白水平、p-IκBα/IκBα比值、p-p65/p65比值显著降低(P均<0.05)。结论 OPC可抑制TLR 4/NF-κB通路,以减轻链脲佐菌素诱导DKD大鼠模型肾损伤、炎症反应。
Abstract
Objective To study the effect of oligomeric procyanidins on renal function protection and inflammation inhibition in diabetic kidney disease rats by inhibiting TLR 4/NF- κB pathway. Methods DKD rat models were established by intraperitoneal injection of streptozotocin (50 mg/kg) and high fat and high sugar diet, and then, low-, medium- and high- doses of OPC (125, 250 and 500 mg/kg) were administered orally to treat DKD rats. After 8 weeks, the blood glucose level, renal index, urinary microalbumin, blood urea nitrogen, and blood creatinine were measured. The levels of IL-1β, IL-6 and MCP-1in serum and renal cortex were detected by ELISA kit. The protein level of TLR 4/NF- κ B related were measured by Western blot. Results Compared with the model group, the pathological state of glomeruli in the low-, middle- and high-dose group of OPC was significantly improved. The fasting blood glucose, renal index, urine albumin protein, serum creatinine and blood urea nitrogen levels of the rats in the medium dose and high dose OPC groups were significantly lower than those in the model group (P<0.05) . The levels of IL-1β, IL-6 and MCP-1 were significantly lower than those in the model group (P<0.05). The result of western blot analysis showed that compared with the model group, the protein level of TLR4 and ratio of p-IκBα/IκBα of rats in OPC medium dose group and OPC high dose group decreased significantly (P<0.05). Conclusions OPC can inhibit TLR 4/NF- κ B pathway, and reduce renal function damage and inflammatory reaction of DKD rat model.
关键词
低聚原花青素 /
糖尿病肾病 /
TLR4/NF-κB通路 /
炎症反应
Key words
oligomeric procyanidins /
diabetic kidney disease /
TLR4/NF- κB pathway /
inflammatory response
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基金
天津市科技计划项目(13JCYBJC24400)
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