氯化亚锡对糖尿病自发性高血压大鼠血压的影响

目的探讨氯化业锡(SnCl_2)对糖尿病自发性高血压大鼠(DSHR)血压的影响及其机制。方法 40只自发性高血压大鼠(SHR)分4组,分别为SHR组、DSHR组、SHR+SnCl_2组以及DSHR+SnCl_2组。SHR共20只,其中10只为SHR+SnCl_2组。通过注射链佐霉素(STz)制造DSHR模型共20只,其中10只为DSHR+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血红素氧合酶(HO)-1、HO-2、凋亡相关蛋白(Bcl)-2表达量,测定HO活性,血浆脂联素水平,股动脉血管内皮反应性,股动脉超氧阴离子(O_2~-)、3硝基酪氨酸(3-NT)水平以及循环系统内皮细胞计数(CEC)。结果 DSHR组血压水平[收缩压(152.1±9.4)mm Hg比(127.0±6.6)mm Hg,P0.05]、氧化应激水平[O_2~-水平(9.33±2.58)×10~4次·min~(-1)·mg~(-)蛋白比(4.13±1.87)×10~4次·min~(-1)·mg~(-1)蛋白,P0.05]、CEC水平[(45±4)个/ml比(30±4)个/ml,P0.05]显著高于SHR组,而血浆脂联素水平[(5.3±1.2)g/L比(10.5±1.1)g/L,P0.05]及股动脉血管内皮反应性显著低于SHR组。SnCl_2显著上调HO-1及Bcl-2表达,增强HO活性[(0.402±0.21)nmol胆红素·mg~(-1)·h~(-1)比(0.12±0.02)nmol胆红素·mg~(-1)·h~(-1),P0.05]、脂联素水平[(20.5±3.0)g/L比(5.3±1.2)g/L,P0.05]及股动脉血管内皮反应性,降低氧化应激[O_2~-水平(5.33±2.14)×10~4次·min~(-1)·mg~(-1)蛋白比(9.33±2.58)×10~4次·min~(-1)·mg~(-1)蛋白,P0.05]及CEC水平[(15±5)个/ml比(45±4)个/ml,P0.05],并显著降低DSHR血压水平[收缩压(127.1±9.0)mmHg比(152.1±9.4)mmHg,P0.05]。结论 SnCl_2通过上调HO-1的表达以及增强HO活性,同时升高血浆脂联素水平,减轻氧化应激水平,改善血管内皮功能,从而降低DSHR血压水平。

Impacts of stannous chloride on the blood pressure of diabetic spontaneously hypertensive rats

Objective To investigate the effects and mechanism of stannous chloride （SnCl2 ） on the blood pressure of diabetic spontaneously hypertensive rats （DSHR）. Methods 40 spontaneously hypertensive rats （SHR） were divided into 4 groups-DSHR group, DSHR ＋ SnCl2 group, SHR group and SHR ＋ SnCl2 group. Twenty DSHR models were made via the injection of streptozotocin （STZ） （65 mg/kg body weight）, including 10 for the DSHR ＋ SnCl2 group （5 mg/ 100 g BW was given subcutaneously, once a week for 4 weeks）. There were 20 rats in SHR group, including 10 SHR ＋ SnCl2 （5 mg/100 g BW was given subcutaneously, once a week for 4 weeks）. The tail artery blood pressure was measured in each group. The heine oxygenase （HO）-1, HO-2 and Bcl-2 expression in femoral artery were measured by Western blot. Also, HO activity, plasma adiponectin level and circulating endothelial cells （CEC）, endothelium reactivity, superoxide anion （O2^-）, nitrotyrosine （3-NT） levels in femoral artery were measured. Results Compared with SHR group, the blood pressure levels [ SBP（ 152. 1 ± 9.4） mm Hg vs. （ 127.0 ± 6. 6） mm Hg, P 〈 0. 05 ], oxidative stress levels [ （ O2^- level （9. 33 ±2. 58） CPM × 10^4/mg protein vs. （4. 13 ± 1.87） CPM × 10^4/mg protein,P 〈0. 05 ], and CEC [ （45 ±4）/ ml vs. （30 ± 4）/ml,P 〈 0. 05 ] were significantly higher in DSHR group, whereas the expressions of HO-1 and Bcl-2, plasma adiponectin levels [ （5.3 ± 1.2） g/L vs. （ 10. 5 ± 1.1 ） g/L,P 〈0. 05 ] and endothelium reactivity in femoral artery were significantly lower. The treatment of SnCl2 significantly upregulated the expressions of HO-1 and Bcl-2, and increased HO activity [ （0. 402 ± 0. 21 ） nmol bilirubin ·mg^-1 · h ^-1 vs. （ 0. 12 ± 0. 02 ） nmol bilirubin ·mg^ -1· h ^-1, p 〈 0. 05 ], adiponectin levels [ （20. 5 ± 3 ） g/L vs. （5.3 ± 1.2） g/L, P 〈 0. 05 ] and endothelium reactivity in femoral artery. It also reduced oxidative stress [ （O2^- level （5. 33 ±2. 14） CPM × 10^4/mg protein vs. （9. 33 ±2. 58） CPM × 10^4/mg protein,P 〈 0.05 ] and CEC [ （ 15 ± 5 ）/ml vs. （45 ± 4 ）/ml, P 〈 0. 05 ], and significantly lowered the blood pressure levels [ SBP （127.1±9.02） mm Hg vs. （152.1±9.4） mmHg,P〈0.05] inDSHR （P〈0.05）. Conclusions SnCl2 reduees DSHR blood pressure levels through upregulating HO-1 expression, increasing HO activity, elevating plasma adiponectin levels, reducing oxidative stress levels, and improving endothelial function.