外源性硫化氢对早期糖尿病肾脏疾病大鼠丝裂原活化细胞外信号调节蛋白激酶/细胞外信号调节激酶信号通路的影响  

Effect of exogenous hydrogen sulfide on mitogen activated extracellular signal regulatory protein kinase/extracellular signal regulatory kinase signaling pathway in early diabetic nephropathy rats

作　　者：陈剑虹 杨少娟 许腾 江燕丽 邓雨欣 胡军[1] Chen Jianhong;Yang Shaojuan;Xu Teng;Jiang Yanli;Deng Yuxin;Hu Jun(Department of Endocrinology,Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430077,China)

机构地区：[1]华中科技大学同济医学院附属梨园医院内分泌科,武汉430077

出　　处：《临床内科杂志》2023年第4期268-272,共5页Journal of Clinical Internal Medicine

摘　　要：目的研究外源性硫化氢(H2 S)通过丝裂原活化细胞外信号调节蛋白激酶(MEK)/细胞外信号调节激酶(ERK)信号通路对早期糖尿病肾脏疾病(DN)大鼠的保护作用。方法随机选取SPF级健康雄性SD大鼠24只腹腔一次性注射1%链尿佐菌素(STZ)60 mg/kg制作DN模型,余下10只(正常对照组)腹腔一次性注射等量的柠檬酸缓冲液。3周后DN造模成功,再将24只DN大鼠随机分为DN组和DN+硫氢化钠(NaHS)组,每组各12只。DN+NaHS组予腹腔注射NaHS溶液56μmol·kg^(-1)·d^(-1),正常对照组和DN组予等量生理盐水腹腔注射,3组大鼠均连续注射12周。检测各组血清肌酐(SCr)、尿素氮(BUN)及24小时尿蛋白(24h Upro)水平,观察其肾脏组织病理变化。采用Katafuchi评分评估大鼠肾脏病变(包括肾小球、肾小管及肾血管)。采用免疫组化法检测ERK1/2、MEK1和MEK2蛋白阳性区域面积百分比。结果DN组大鼠SCr、BUN及24h Upro水平、肾脏组织Katafuchi评分、MEK1、MEK2及ERK1/2蛋白阳性区域面积百分比均显著高于正常对照组和DN+NaHS组(P<0.01),而正常对照组与DN+NaHS组大鼠上述指标水平比较差异均无统计学意义(P>0.05)。结论外源性H2 S对早期DN大鼠肾脏的保护作用可能与抑制MEK/ERK信号通路有关。Objective To investigate the protective effect of exogenous hydrogen sulfide(H2 S)on early diabetic nephropathy(DN)rats through mitogen activated extracellular signal regulatory protein kinase(MEK)/extracellular signal regulatory kinase(ERK)signaling pathway.Methods Twenty⁃four healthy male SPF SD rats were randomly selected and injected with 1%streptomycin(STZ)60 mg/kg in the abdominal cavity to make model of DN,and the remaining 10 rats(normal control group)were injected with citrate buffer in the abdominal cavity.3 weeks later,DN modeling was successful,and then 24 DN rats were randomly divided into DN group and DN+NaHS group with 12 rats in each group.DN+NaHS group was given intraperitoneal injection of NaHS solution 56μmol·kg^(-1)·d^(-1),normal control group and DN group were given intraperitoneal injection of normal saline.The levels of serum creatinine(SCr),urea nitrogen(BUN)and 24⁃hour urinary protein(24h Upro)in each group were detected after continuous injection for 12 weeks.The pathological changes of kidney tissue in each group were observed.Katafuchi score was performed for renal lesions(including glomeruli,renal tubules and renal vessels)in rats.The percentage of ERK1/2,MEK1 and MEK2 protein positive area was detected by immunohistochemical method.Results The levels of SCr,BUN and 24h Upro,Katafuchi score of kidney tissue,the percentage of MEK1,MEK2 and ERK1/2 protein positive area in DN group were significantly higher than those in normal control group and DN+NaHS group(P<0.01).There was no significant difference in the above indexes between normal control group and DN+NaHS group(P>0.05).Conclusion Exogenous H2 S to the early DN rat renal protective effect may be related to the inhibition of MEK/ERK signaling pathway.

关 键 词：糖尿病 硫化氢 糖尿病肾脏疾病 丝裂原活化细胞外信号调节蛋白激酶/细胞外信号调节激酶信号通路 

分 类 号：R587.2[医药卫生—内分泌]