血红素加氧酶1对2型糖尿病肾病大鼠肾脏功能影响的研究  

Effect of HO-1 on renal function of rats with type 2 diabetic nephropathy

作　　者：罗喜钢 王毅 张凤香 Xi-gang Luo;Yi Wang;Feng-xiang Zhang(Clinical Laboratory, the Third Afliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China;Department of Thoracic Surgery, the First Afliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, China)

机构地区：[1]锦州医科大学附属第三医院检验中心,辽宁锦州121000 [2]锦州医科大学附属第一医院胸外科,辽宁锦州121001

出　　处：《中国现代医学杂志》2018年第16期1-5,共5页China Journal of Modern Medicine

基　　金：国家自然科学基金(No:81541099)

摘　　要：目的通过复制糖尿病肾病大鼠模型,以药物干预改变糖尿病肾病大鼠肾脏中血红素加氧酶1(HO-1)水平,从而探讨HO-1对2型糖尿病肾病大鼠肾脏功能的影响。方法 32只SD大鼠适应性喂养1周后,随机分成正常对照组、糖尿病肾病(DN)组、DN氯化血红素组和DN锌原卟啉组。除正常对照组外,其他3组复制糖尿病肾病模型,进行药物干预。各组大鼠用药4周后进行取材,大鼠处死前禁食收集24 h尿液,测定大鼠24 h尿量和尿肌酐(Ucr)。大鼠麻醉后心脏取血,分别检测血肌酐(Scr)和血胱抑素C(Cys-c)的浓度,计算内生肌酐清除率(Ccr)。肾脏组织HE染色观察大鼠肾脏组织结构是否异常,电镜下观察肾小球和肾小管超微结构的改变,应用免疫组织化学和Western blot技术对肾脏中HO-1进行定位和定量分析。结果(1)DN组、DN氯化血红素组和DN锌原卟啉组Scr、Cys-c、Ucr、Ccr与正常对照组比较,差异有统计学意义(P<0.05),DN组、DN氯化血红素组和DN锌原卟啉组Scr和Cys-c升高,Ucr、Ccr降低,DN锌原卟啉组Scr和Cys-c增加幅度较DN组和DN氯化血红素组高。(2)HE染色及电镜结果显示,正常对照组大鼠肾脏组织结构无明显变化,其余3组大鼠肾脏组织结构均有改变。肾脏组织结构破坏程度,DN锌原卟啉组>DN组>DN氯化血红素组。(3)Western blot结果显示,DN氯化血红素组肾脏中HO-1表达水平高于DN组,DN锌原卟啉组肾脏中HO-1表达水平低于DN组。结论 DN氯化血红素组大鼠肾脏中HO-1表达水平升高,而DN锌原卟啉组大鼠肾脏中HO-1表达水平下降,DN氯化血红素组大鼠肾脏的损伤指标以及肾脏组织形态学的损伤程度轻于DN锌原卟啉组,实验结果说明提高2型糖尿病肾病大鼠肾脏中HO-1表达水平可以减轻肾脏损伤。Objective To investigate the effect of heme oxygenase-1（HO-1） on the renal function of rats with type 2 diabetic nephropathy by changing the expression of HO-1 in the kidneys of the rats through drug intervention. Methods After one week of adaptive feeding, 32 SD rats were randomly divided into normal control group, diabetic nephropathy（DN） group, DN hemin group and DN zinc protoporphyrin group with 8 in each group. The rats in each group were sacrificed 4 weeks later. The rats were fasted before sacrifice to collect 24-h urine. The volume of 24-h urine and urinary creatinine（Ucr） were measured. Blood samples were taken from the hearts of the rats after anesthesia. Serum creatinine（Scr） and blood cystatin C（Cys-C） concentrations were measured and the creatinine clearance rate（Ccr） was calculated. HE staining was used to observe the histological changes of renal tissues. The ultrastructural changes of glomeruli and renal tubules were observed by electron microscopy. Immunohistochemistry and Western blot were used for localization and quantitative analysis of HO-1 in the rat kidneys. Results Compared with the control group, the levels of Scr and Cys-C were increased（P〈0.05）, Ucr and Ccr were decreased（P〈0.05） in the DN group, the DN hemin group and the DN zinc protoporphyrin group; Scr and Cys-C increased more in the DN zinc protoporphyrin group than in the DN and DN hemin groups. HE staining and electron microscopy showed that the renal tissue structures of the control group had no obvious change, but the structures of the kidney tissues changed in the other three groups. The degree of renal tissue structure damage was ranged as follows： DN zinc protoporphyrin group DN group DN hemin group. Western blot analysis showed that the expression of HO-1 in the kidneys of the DN hemin group was higher than that in the DN group, and the expression of HO-1 in the DN zinc protoporphyrin group was lower than that in the DN group. Conclusions The expression of HO-1 significantly increased

关 键 词：2型糖尿病肾病 血红素加氧酶1 内生肌酐清除率 肾损伤 

分 类 号：R-332[医药卫生]