固本通络方对Ig A肾病小鼠炎症反应、氧化应激和TGF-β1/Smads信号通路的影响

Effects of Guben Tongluo Formula on Inflammatory Response, Oxidative Stress and TGF-β1/Smads Signaling Pathway in Ig A Nephropathy Mice

目的:研究固本通络方对免疫球蛋白A(Ig A)肾病小鼠炎症反应、氧化应激和转化生长因子β1(TGF-β1)/Smads信号通路的影响。方法:选取45只雄性昆明种小鼠作为研究对象。以电脑随机数字表法将其分为正常组、模型组以及治疗组,每组各15只。模型组及治疗组均通过牛血清白蛋白及葡萄球菌肠毒素B进行诱导造模,造模结束后,治疗组给予固本通络方灌胃干预,模型组及正常组均给予生理盐水灌胃处理。对比三组肾脏病理损伤以及系膜区Ig A沉积、肾脏损伤指标、炎症反应指标、氧化应激反应指标、Peyer小结TGF-β1/Smads信号通路指标。结果:正常组无异常肾脏病理变化,模型组及治疗组均可见显著肾小球系膜细胞增生以及基质增多,系膜区有免疫复合物沉积,治疗结束后治疗组相较于模型组肾小球病变显著减轻。正常组系膜区无Ig A沉积,模型组及治疗组均可见系膜区明显团块状或颗粒状中等强度Ig A沉积,且在治疗后治疗组相较于模型组系膜区Ig A沉积有所减弱。三组血肌酐(Scr)及尿素氮(BUN)水平对比无明显差异(均P>0.05);模型组及治疗组24 h尿蛋白定量均高于正常组,且治疗组24 h尿蛋白定量低于模型组(均P<0.05)。模型组、治疗组血清白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平均高于正常组,且治疗组上述各项血清学指标水平均低于模型组(均P<0.05)。模型组、治疗组MDA均高于正常组,而治疗组MDA低于模型组;模型组、治疗组SOD均低于正常组,而治疗组SOD高于模型组(均P<0.05)。模型组、治疗组Peyer小结TGF-β1、Smad3蛋白表达量均高于正常组,且治疗组上述蛋白表达量低于模型组(均P<0.05)。结论:固本通络方可有效改善Ig A肾病小鼠炎症反应、氧化应激,可能和调控TGF-β1/Smads信号通路有关。

Objective: To study the effects of Guben Tongluo formula on inflammatory response, oxidative stress and transforming growth factor β1(TGF-β1)/Smads signaling pathway in immunoglobulin A(Ig A) nephropathy mice. Methods: 45 male Kunming mice were selected as the research objects. They were divided into normal group, model group and treatment group by computer random number table, 15 rats in each group. The model group and the treatment group were induced modeling by bovine serum albumin and staphylococcal enterotoxin B. After modeling, the treatment group was given Guben Tongluo formula by gavage intervention, and the model group and the normal group were given normal saline by gavage treatment. Renal pathological injury, mesangial Ig A deposition, renal injury index, inflammatory response index, oxidative stress response index, Peyer summary TGF-β1/Smads signaling pathway index were compared in the three groups. Results: There were no abnormal renal pathological changes in the normal group, but there were significant mesangial cell hyperplasia and matrix increase in the model group and the treatment group, and immune complex deposition in the mesangial area. After treatment, the glomerular lesions in the treatment group were significantly reduced compared with the model group.There was no Ig A deposition in the mesangial area in the normal group, but the mesangial area in the model group and the treatment group was significantly clumped or granular with moderate intensity Ig A deposition, and the mesangial Ig A deposition was decreased in the treatment group after treatment compared with the model group. There were no significant differences in serum creatinine(Scr) and blood urea nitrogen(BUN) levels in the three groups(all P>0.05). The 24 h urinary protein quantification in the model group and the treatment group were higher than that in the normal group, and the 24 h urinary protein quantification in the treatment group was lower than that in the model group(all P<0.05). The serum interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α)levels in the model group and treatment group were higher than those in the normal group, and the serum levels of the above-mentioned serological indexes in the treatment group were lower than those in the model group(all P<0.05). The MDA in the model group and treatment group was higher than that in the normal group, while the MDA in the treatment group was lower than that in the model group.SOD in the model group and treatment group was lower than that in the normal group, while SOD in the treatment group was higher than that in the model group(all P<0.05). The protein expressions of TGF-β1 and Smad3 in the model group and treatment group were higher than those in the normal group, and the protein expressions in the treatment group were lower than those in the model group(all P<0.05).Conclusion: Guben Tongluo formula can effectively improve the inflammatory response and oxidative stress in Ig A nephropathy mice,which may be related to the regulation of TGF-β1/Smads signaling pathway.