【摘要】 目的:探讨番茄红素对糖尿病肾病(DN)大鼠内质网应激(ERS)的影响。方法:采用高糖高脂饲料喂养加腹腔注射链尿佐菌素的方法制备DN大鼠模型,50只造模成功的大鼠随机分为模型组,四苯基丁酸组和番茄红素低、中、高剂量组,每组10只,另设10只未造模大鼠作为正常对照组。四苯基丁酸组和番茄红素低、中、高剂量组分别灌胃相应药物进行治疗,模型组灌胃等体积生理盐水,模型组和正常对照组灌胃等体积生理盐水,1次/d,连续8周。分别于给药前及给药后第7、14、28、56天检测空腹血糖水平;治疗完成后,测定24 h尿蛋白量(UPro)和血清尿素氮(BUN)、肌酐(SCr)含量,HE染色法行肾组织病理学检查,TUNEL法观察肾细胞凋亡,ELISA法检测肾组织C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)水平,Western blotting法检测肾组织糖调节蛋白78(GRP78)、增强子结合蛋白同源蛋白(CHOP)、核因子-κB(NF-κB)、半胱氨酸天冬氨酸蛋白酶-12(Caspase-12)表达。结果:与模型组比较,四苯基丁酸组和番茄红素中、高剂量组给药4周后空腹血糖水平降低(P<0.05或P<0.01);给药8周后UPro和血清中BUN、SCr含量降低(P<0.01);肾组织病理性形态结构改变明显改善,肾细胞凋亡指数(AI)降低(P<0.01);肾组织CRP、TNF-α、IL-1β水平降低(P<0.01),GRP78、CHOP、NF-κB、Caspase-12表达下调(P<0.01)。与四苯基丁酸组比较,番茄红素高剂量组空腹血糖水平和肾细胞AI降低(P<0.05或P<0.01),两组间其他指标比较,差异均无统计学意义(P>0.05)。结论:番茄红素能够通过抑制ERS通路及其介导的炎症反应和细胞凋亡对DN大鼠肾损伤起到保护作用。更多还原

【Abstract】 Objective: To investigate the effect of lycopene on endoplasmic reticulum stress(ERS) in diabetic nephropathy(DN) rats. Methods: The DN rat model was prepared by feeding with high-sugar and high-fat feed and intraperitoneal injection of streptozotocin. 50 rats with successful modeling were randomly divided into model group, tetraphenylbutyric acid group and lycopene low-dose group, lycopene medium-dose group and lycopene high-dose group, with 10 rats in each group, and 10 rats without modeling were set as normal control group.Rats in the tetraphenylbutyric acid group and lycopene low, medium and high-dose groups were treated with corresponding drugs by gavage respectively. Rats in the model group and the normal control group were given the same volume of normal saline, once a day for 8 weeks. The fasting blood glucose levels were measured before administration and on the 7, 14, 28, and 56 days after administration. After the treatment, the 24 h urine protein content(UPro), serum urea nitrogen(BUN) and creatinine(SCr) content were measured. The renal histopathological examination was performed by HE staining method, and renal tissue cell apoptosis was observed by TUNEL.The levels of C-reactive protein(CRP), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) in renal tissue were detected by ELISA method. The expression of glycoregulated protein 78(GRP78), enhancer binding protein homologous protein(CHOP), nuclear factor-κB(NF-κB), cysteine protease-12(Caspase-12) in renal tissue were detected by Western blotting method. Results: Compared with model group, the fasting blood glucose levels of rats in tetraphenylbutyric acid group and lycopene medium, high-dose group were decreased after 4 weeks of administration(P<0.05 or P<0.01). After 8 weeks of administration, the levels of BUN and the content of BUN,SCr in serum were decreased(P <0.01). The pathological morphological and structural changes of renal tissue were significantly improved, and the renal cells apoptosis index(AI) was decreased(P<0.01). The levels of CRP,TNF-α, IL-1β in renal tissue were decreased(P<0.01), and the expression of GRP78, CHOP, NF-κB, Caspase-12 down-regulated(P<0.01). Compared with the tetraphenylbutyric acid group, the fasting blood glucose level and AI of renal cell in lycopene high-dose group was decreased(P<0.05 or P<0.01). There was no significant difference in other indicators between the two groups(P>0.05). Conclusion: Lycopene can protect DN rats from renal injury by inhibiting the ERS signaling pathway and its mediated inflammatory response and cell apoptosis.更多还原