高同型半胱氨酸血症对紫癜性肾炎CBS<sup>+/-</sup>小鼠足细胞损伤的影响及机制

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摘要 目的: 研究高同型半胱氨酸血症（hyperhomocysteinemia,HHcy）诱导过敏性紫癜（Henoch-Schonlein purpura,HSP）胱硫醚-β-合酶（cystathionine -β- synthase,CBS）杂合突变（CBS^+/-）小鼠足细胞损伤的作用及机制。方法: 野生型CBS（CBS^+/+）小鼠及CBS^+/-小鼠均采用印度墨水尾静脉注射、小麦醇溶蛋白灌胃及尾静脉注射的方式进行紫癜性肾炎（HSP nephritis,HSPN）造模,造模过程中给予常规饮食或高蛋氨酸饮食。比较各组小鼠血清同型半胱氨酸（homocysteinemia,Hcy）含量、肾脏病理改变及超微结构改变、血肌酐（Scr）、尿素氮（BUN）、24h尿蛋白、Podocin、Nephrin、Podocalyxin表达水平的差异。结果: 常规饮食CBS^+/++HSPN组、高蛋氨酸饮食CBS^+/++HSPN组均出现肾脏病理改变,且Scr、BUN、24h尿蛋白水平均高于常规饮食CBS^+/+组,但高蛋氨酸饮食CBS^+/++HSPN组的肾脏病理改变及Scr、BUN、24h尿蛋白水平与常规饮食CBS^+/++HSPN组比较无显著性差异。常规饮食CBS^+/-+HSPN组出现肾脏病理改变及超微结构改变,Scr、BUN、24h尿蛋白水平高于常规饮食CBS^+/-组,Podocin、Nephrin、Podocalyxin的表达水平低于常规饮食CBS^+/-组;与常规饮食CBS^+/-+HSPN组比较,高蛋氨酸饮食CBS^+/-+HSPN组的肾脏病理改变及超微结构改变加重,Hcy、Scr、BUN、24h尿蛋白水平升高,Podocin、Nephrin、Podocalyxin的表达水平降低;与高蛋氨酸饮食CBS^+/-+HSPN组比较,叶酸+高蛋氨酸饮食CBS^+/-+HSPN组的肾脏病理改变及超微结构改变减轻,Hcy、Scr、BUN、24h尿蛋白水平降低,Podocin、Nephrin、Podocalyxin的表达水平升高。结论: HHcy促进HSPN CBS^+/-小鼠肾脏病理改变、足细胞损伤加重,抑制跨膜蛋白Podocin、Nephrin、Podocalyxin表达是可能的分子机制。

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	郭宝珠

关键词 ：过敏性紫癜, 紫癜性肾炎, 高同型半胱氨酸血症, 胱硫醚-β-合酶, 足细胞损伤

Abstract：Objective To study the effect and mechanism of homocysteinemia (HHcy) - induced podocyte injury in Henoch Schonlein purpura nephritis (HSPN) cystathionine -β- synthase (CBS) heterozygous mutation (CBS^+/-) mice. Methods HSPN model was established in wild type CBS (CBS^+/+) mice and CBS^+/-mice, then given conventional diet or high methionine diet respectively. The levels of serum Hcy, renal pathological and ultrastructural changes, serum creatinine (Scr), blood urea nitrogen (BUN), 24-hour urinary protein, the expression of podocin, nephrin and podocalyxin were compared. Results The renal pathological changes were found in the CBS^+/++HSPN group and the high methionine diet CBS^+/++HSPN group, and the levels of Scr, BUN and 24h urinary protein were higher than those in the conventional diet CBS^+/+group, but there was no significant difference in the renal pathological changes, Scr, BUN and 24h urinary protein levels between the high methionine diet CBS^+/++HSPN group and the conventional diet CBS^+/++ HSPN group. Renal pathological and ultrastructural changes were observed in conventional diet CBS^+/-+HSPN group, Scr, BUN and 24h urinary protein levels were higher than those of conventional diet CBS^+/- group, the expression of podocin, nephrin and podocalyxin were lower than those of conventional diet CBS^+/- group; compared with conventional diet CBS^+/-+HSPN group, renal athological and ultrastructural changes aggravated, Hcy, Scr, BUN and 24h urinary protein levels increased, the expression of podocin, nephrin and podocalyxin decreased of high methionine diet CBS^+/- group; compared with high methionine diet CBS^+/- group, renal athological and ultrastructural changes improved, Hcy, Scr, BUN and 24h urinary protein levels decreased, the expression of podocin, nephrin and podocalyxin increased in folic acid+ high methionine diet CBS^+/- group. Conclusion HHcy can promote renal pathological changes and podocyte injury in HSPN CBS^+/- mice, and inhibit the expression of transmembrane proteins podocin, nephrin and podocalyxin is a possible molecular mechanism.

Key words： Henoch Schonlein purpura Henoch Schonlein purpura nephritis hyperhomocysteinemia cystathionine β- synthase podocyte injury

收稿日期: 2022-07-22

中图分类号:

R363

基金资助:张家口市科技攻关计划项目（1921042D）; 2022年度河北省医学科学研究课题计划（20220602）

通讯作者: 陈雷刚,E-mail：Lchen45683587@163.com

引用本文:

陈雷刚, 杨晓静, 冯冬梅, 吴远慧, 王世宁, 郭宝珠. 高同型半胱氨酸血症对紫癜性肾炎CBS^+/-小鼠足细胞损伤的影响及机制[J]. 湖南师范大学学报(医学版), 2023, 20(4): 11-17. CHEN Leigang, YANG Xiaojing, FENG Dongmei, WU Yuanhui, WANG Shining, GUO Baozhu. Effect and mechanism of hyperhomocysteinemia induced podocyte injury in Henoch Schonlein purpura nephritis CBS^+/- mice. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(4): 11-17.

链接本文:

http://yxb.hunnu.edu.cn/CN/ 或 http://yxb.hunnu.edu.cn/CN/Y2023/V20/I4/11

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