上调血红素氧合酶-1对实验性糖尿病大鼠血管内皮功能及血压的影响  

Effect of up-regulated heme-oxygenase-1 level on the vascular endothelial function and blood pressure in experimental diabetic rats

作　　者：朱冰坡[1] 曹剑[1] 李健[1] 王浩[1] 石海燕[1] 范利[1] 

机构地区：[1]解放军总医院南楼心血管一科,北京100853

出　　处：《武警医学》2011年第6期490-494,共5页Medical Journal of the Chinese People's Armed Police Force

基　　金：军队"十一五"保健课题项目(编号:09BJZ01)

摘　　要：目的探讨应用氯化亚锡(SnCl_2)上调血红素氧合酶-1(HO-1)对实验性糖尿病大鼠血管内皮功能及血压的影响及其机制。方法 40只Wistar-Kyoto(WKY)大鼠分为4组,分别为WKY组、糖尿病大鼠(DWKY)组、WKY+SnCl_2组及DWKY+SnCl_2组。通过注射链佐霉素(STZ)制造DWKY模型共20只,其中10只进一步制作为DWKY+SnCl_2组。WKY组共20只,其中10只进一步制作为WKY+SnCl_2组。分别测量各组大鼠尾动脉血压,采用免疫印迹法测定股动脉HO-1、HO-2、凋亡相关蛋白(Bcl-2)表达量,HO活性,环氧化酶2(COX-2)水平,脂联素、肿瘤坏死因子-α(TNF-α)、超氧阴离子(O_2^-)水平,股动脉血管内皮反应性以及循环内皮细胞计数(CEC)。结果 DWKY组中股动脉血管内皮反应性显著低于WKY组。SnCl_2显著上调HO-1及Bcl-2表达,降低COX-2水平,增加HO活性[0.25±0.05 nmol胆红素/(mg·h)与0.17±0.025 nmol胆红素/(mg·h),P<0.05],降低O_2^-、TNF-α水平,增加脂联素水平及股动脉血管内皮反应性,显著减少内皮细胞脱落并显著降低DWKY血压水平(收缩压100±1 mmHg与81±2 mmHg,P<0.05)。结论 SnCl_2通过上调HO-1的表达以及增加HO活性,升高脂联素水平,同时改善血管内皮功能,从而降低糖尿病大鼠的血压水平。Objective To investigate the effect of up - regulated heine - oxygenase - 1 （ HO - 1 ） levels on the vascular endo- thelial function and blood pressure in experimental diabetes mellitus. Methods 40 Wistar - Kyoto rats （WKY） were divided into 4 groups ：diabetic WKY （DWKY） group, DWKY ＋ stannous chloride （ SnCI2） group, WKY group and WKY ＋ SnCI2 group. 20 DWKY models were established through injections of streptozotocin （STZ） , including 10 for the DWKY ＋ SnC12 group. There were 20 rats in WKY group, including 10 WKY ＋ SnCI2 rats. The tail artery blood pressure was measured in each group. HO - 1, HO -2 and Bcl - 2 expression of the femoral artery were measured by Western bloting. HO activity, cyclooxygenase 2 （ COX - 2） level, adiponectin, tumor necrosis factor - α （TNF - α）, superoxide anion （ O2- ） ,circulating endothelial cells （ CEC）, and endothelium reactivity of the femoral artery were also measured. Results The endothelium reactivity in the femoral artery was significantly lower in the DWKY group than that in the WKY group. The treatment with SnC12 significantly upregulated HO - 1 and Bcl -2 expressiun, decreased the level of COX -2, and increased HO activity （0. 25 -＋0. 05 nmol bilirubin/mg/h vs 0. 17 ±0. 025 nmol bilirubin/mg/h,P 〈0. 05） and endothelium reactivity in the femoral artery.. It also significantly decreased adiponectin, TNF-±, 02- , CEC and blood pressure levels （SBP 100 ±1 mm Hg vs 81 ± 2 mm Hg,P 〈 0. 05） in DWKY rats（P 〈 0. 05 ）. Conclusion SnC12 reduces blood pressure levels by upregulating HO - 1 expression, increasing HO activity and adiponectin level, and improving endothelial func.tion in diabetic rats.

关 键 词：氯化亚锡 血红素氧合酶 高血压 糖尿病 

分 类 号：R544[医药卫生—心血管疾病]