摘要目的 探讨高压氧(hyperbaric oxygen,HBO)联合固本通络方对IgA肾病(IgA nephropathy,IgAN)小鼠的治疗效果及其分子机制.方法 建立α1K1-CD89 Tg转基因IgAN小鼠模型,按照数字表法随机分为空白对照组、模型组、骨化三醇组、中药组和中药+HBO组,观察各组小鼠外周血IgA1、异常糖基化IgA1、白介素-6(interleukin 6,IL-6)及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α的表达水平;检测肠黏膜C1GalT1、伴侣蛋白Cosmc的表达及肾脏损伤情况[尿蛋白、血肌酐(Scr)及尿素氮(BUN)].结果 与空白对照组治疗前比较,模型组、骨化三醇组、中药组和中药+HBO组小鼠外周血IgA、异常糖基化IgA1、IL-6及TNF-α水平均明显上升(P<0.05),Scr和BUN水平则无明显差异(P>0.05);治疗后,与模型组比较,骨化三醇组、中药组、中药+HBO组小鼠尿蛋白、IgA1、异常糖基化IgA1、IL-6及TNF-α水平均明显降低(P<0.05),且中药组降低程度大于骨化三醇组,但低于中药+HBO组;治疗后各组取小鼠肠黏膜组织,与空白对照组比较,模型组小鼠肠黏膜组织中C1GalT1和Cosmc表达明显降低;与同模型组比较,骨化三醇组、中药组、中药+HBO组C1GalT1和Cosmc表达明显升高(P<0.05),其中以中药+HBO组效果最明显.结论 HBO治疗可增强固本通络方剂对IgAN小鼠的治疗效果,主要通过降低IL-6及TNF-α的表达、抑制B细胞的异常激活、并促进CIGALT1和Cosmc的表达实现.

abstractsObjective To investigate the therapeutic effect hyperbaric oxygen ( HBO) combined with Gubentongluofang on IgA nephropathy ( IgAN) in mice and possible molecular mechanism involved .Methods The murine α1k1-CD89 Tg transgene IgAN model was developed , and the animals were randomly divided into the control group , the model group , the calcitriol group , the Chinese herbal medicine group and the Chinese herbal medicine +HBO group.The expression levels of IgA, abnormal glycosylated IgA1, interleukin 6 ( IL-6 ) and tumor necrosis factor-α( TNF-α) of peripheral blood were detected , and the expressions of C1GalT1 and Cosmc protein in intestinal mucosa , kidney damage ( urine protein, serum creatinine and urea nitrogen) and blood urea nitrogen ( BUN) as well were detected for further analyses .Results As compared with those of the control group before treatment , the levels of IgA, abnormal glycosylation IgA1, IL-6 and TNF-in peripheral blood were significantly increased in the model group , the calcitriol group , the Chinese herbal medicine group and the Chinese herbal medicine +HBO group (P<0.05), and no significant differences could be noted in the levels of Scr and BUN in various groups ( P >0.05).After treatment, the levels of urine protein, IgA1, abnormal glycosylated IgA1, IL-6 and TNF-all significantly reduced in the calcitriol group , the Chinese herbal medicine group and the Chinese herbal medicine +HBO group, as compared with the model group(P<0.05), and the rate of reduction in the Chinese herbal medicine group was greater than that of the calcitriol group, but lower than that of the Chinese herbal medicine +HBO group (P<0.05).Intestinal mucosal tissues of the mice in various groups were collected after treatment for further analyses .As compared with the control group , C1GalT1 and Cosmc expression levels in intestinal mucosa in the model group decreased significantly.When compared with those in the model group , the C1GalT1 and Cosmc expression levels in the calcitriol group , the Chinese herbal medicine group , as well as the Chinese herbal medicine +HBO group increased considerably , with the increase in the Chinese herbal medicine +HBO group being most significant (P<0.05).Conclusion HBO could enhance the therapeutic effect of Gubentongluofang on IgAN , it might be closely associated with the down-regulation of IL-6 and TNF-and inhibition of abnormal activation of B cells and promotion of CIGALT1 and Cosmc expression .