机构地区:[1]河南中医药大学,河南郑州450046 [2]河南中医药大学第一附属医院,河南郑州450000 [3]鄢陵县中医院,河南许昌461200 [4]信阳市中心医院,河南信阳464000
出 处:《中华中医药学刊》2022年第10期129-132,I0023,I0024,共6页Chinese Archives of Traditional Chinese Medicine
基 金:国家自然科学基金(82074493);河南省自然科学基金面上项目(2023004102);河南省中医药文化著作出版专项(TCMCB2020009);河南省科技攻关重点项目(202102310494);河南省中医管理局国家中医临床研究基地科研专项(2018JDZX119,2018JDZX017);河南省中医药学科领军人才项目(豫卫中医函[2021]8号)。
摘 要:目的 探讨雷公藤多苷(tripterygium wilfordii polyglycosides, GTW)通过影响IgA肾病(immunoglobulin A nephropathy, IgAN)小鼠结肠黏膜病理及血清BAFF/Gd-IgA1表达而减轻肾脏损伤的疗效机制。方法 清洁级雄性Balb/c小鼠40只,适应性喂养1周后,随机分为4组:空白组、IgAN模型组(模型组)、醋酸泼尼松干预组(激素组)、GTW干预组(GTW组),每组10只。除空白组用同等量的蒸馏水灌胃及生理盐水皮下注射外,其余3组均采用BSA+CCL4+LPS法建立IgAN小鼠模型,于造模第3周开始药物灌胃,共6周。动物处死前留取小鼠24 h尿液、血液、肾脏及结肠组织。生化检测各组小鼠24-UTP、Scr、BUN、ALB、ALT;HE染色光镜观察肾组织和结肠黏膜病理改变,免疫荧光判定免疫球蛋白IgA在肾小球系膜区的沉积;ELISA法检测血清BAFF、Gd-IgA1的表达。结果 模型组ALB减少,24-UTP、Scr、BUN及ALT升高,肾脏损伤较重,系膜区IgA沉积强度下降,结肠黏膜炎症明显,与空白组比较,差异具有统计学意义(P<0.05或P<0.01)。GTW组及激素组BAFF、Gd-IgA1的表达下调,ALB升高,24-UTP、Scr、BUN及ALT降低,肾脏病理改善,系膜区IgA沉积减少,结肠炎症性病变减轻,与模型组比较差异具有统计学意义(P<0.05或P<0.01)。GTW组与激素组两组间比较,24-UTP及BAFF表达升高,Scr下降,差异具有统计学意义(P<0.01)。结论 GTW可能通过改善IgAN小鼠结肠炎症反应、影响血清BAFF的表达,抑制Gd-IgA1分泌,从而改善上述生化指标、减轻肾脏病理损害。Objective To explore the therapeutic mechanism of Tripterygium wilfordii polyglycosides(GTW) by affecting the pathology of the colon mucosa of IgA nephropathy(IgAN) mice and the expression of serum BAFF/Gd-IgA1 to reduce kidney injury.Methods Forty clean-grade male Balb/c mice were randomly divided into 4 groups after 1 week of adaptive feeding: blank group, IgAN model group(model group),prednisone acetate intervention group(hormone group),GTW intervention group(GTW group),10 in each group.Except that the blank group was given the same amount of distilled water and subcutaneously injected with normal saline, the other three groups were all used BSA+CCL4+LPS to establish IgAN mouse models.The drug was given to the rats on the third week of model building for 6 weeks.The urine, blood, kidney and colon tissues of the mice were collected for 24 hours before the animals were sacrificed.The levels of 24-hour urinary protein quantitation(24-UTP),serum creatinine(Scr),urea nitrogen(BUN),albumin(ALB) and alanine aminotransferase(ALT) in each group of mice were detected.HE staining light microscope was used to observe the pathological changes of kidney tissue and colon mucosa.The immunofluorescence method was used to determine the deposition of immunoglobulin IgA in the glomerular mesangial area.ELISA method was used to detect the expressions of serum B cell activating factor(BAFF) and galactose-deficient IgA1(Gd-IgA1).Results In the model group, the level of ALB was decreased and the levels of 24-UTP,Scr, BUN and ALT were increased.The kidney damage was severe, IgA deposition intensity in the mesangial area decreased, and colonic mucosal inflammation was obvious.Compared with those of the blank group, there was a statistical difference(P<0.05 or P<0.01).The expressions of BAFF and Gd-IgA1 were down-regulated in the GTW group and the hormone group.Compared with those of the model group, the level of ALB was increased and the levels of 24-UTP,Scr, BUN and ALT decreased.The renal pathology improved, the IgA deposition in the
关 键 词:雷公藤多苷 IgAN 结肠病理 BAFF/Gd-IgA1 肾损伤
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