高压氧联合固本通络方对IgA肾病小鼠的治疗作用  

Effect of hyperbaric oxygen combined with Gubentongluofang on IgA nephropathy in mice

作　　者：沈姣姣[1] 吴卿[1] 黄迪[1] 杨雪军[1] 于秀峙[2] 沈沛成[1] 何立群[1] Shen Jiaojiao;Wu Qing;Huang Di;Yang Xuejun;Yu Xiuzhi;Shen Peicheng;He Liqun(Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China)

机构地区：[1]上海中医药大学附属曙光医院肾病科、上海中医药研究院中医肾病研究所、肝肾疾病病证教育部重点实验室、何立群上海市名中医工作室,上海200021 [2]解放军第四五五医院肾病中心

出　　处：《中华航海医学与高气压医学杂志》2018年第5期305-309,共5页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

基　　金：上海市中医临床重点实验室资助项目（14D22273200）;何立群上海市名老中医学术经验研究工作室资助（SHGZS-2017027）

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。Objective 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 cal

关 键 词：高压氧 固本通络方 IGA肾病 小鼠 

分 类 号：R692.31[医药卫生—泌尿科学]