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目的观察糖尿病肾病(DN)大鼠白细胞介素-18(IL-18)和去氧肾上腺素(nephrin)的表达情况,研究IL-18在DN中的意义及替米沙坦对IL-18和nephrin的影响,探讨其对肾脏的保护机制。方法用链脲佐菌素(STZ)建立DN大鼠模型,将DN模型大鼠随机分为2组:DN模型组和替米沙坦组,另设正常对照组。8周后,观察大鼠体重、肾重、24h尿蛋白定量、血糖、血清尿素氮和肌酐变化;采用免疫组织化学ABC法检测各组大鼠肾组织IL-18和nephrin表达情况。结果 DN模型组大鼠24h尿蛋白定量明显增加,肾功能下降,肾组织IL-18表达明显增多、nephrin表达明显减少(P<0.01),且均与24h尿蛋白定量和肾功能明显相关(P<0.01);经替米沙坦干预后,上述指标明显改善(P<0.05),肾脏病理改变减轻。结论 IL-18可能参与DN的形成;替米沙坦可能通过抑制肾脏炎症反应、减少nephrin损伤来保护肾脏。
Objective To observe the expression of interleukin-18 (IL-18) and nephrin in diabetic nephropathy (DN) rats and to explore the significance of IL-18 in DN and the effect of telmisartan on IL-18 and nephrin influence, to explore its mechanism of protection of the kidneys. Methods DN rat model was established by streptozotocin (STZ). The DN model rats were randomly divided into two groups: DN model group and telmisartan group, and another normal control group. After 8 weeks, the body weight, kidney weight, urinary protein excretion, blood glucose, serum urea nitrogen and creatinine were observed. The expression of IL-18 and nephrin in kidney were detected by immunohistochemical ABC method. Results The proteinuria of 24 h urinary protein in DN model group was significantly increased, the renal function was decreased, the expression of IL-18 in renal tissue was significantly increased and the expression of nephrin was significantly decreased (P <0.01), and both were positively correlated with 24 h urinary protein and renal function <0.01). After the intervention of telmisartan, the above indexes were significantly improved (P <0.05), and the renal pathological changes were alleviated. Conclusion IL-18 may be involved in the formation of DN. Telmisartan may protect the kidneys by inhibiting renal inflammation and reducing nephrin damage.