辛伐他汀对脑缺血-再灌注大鼠神经细胞的保护作用

The protective effect of simvastatin on neurons following local cerebral ischemia-reperfusion in rats

目的探讨辛伐他汀对局灶性脑缺血-再灌注大鼠神经细胞的保护作用及其机制。方法随机将36只大鼠分为3组:即假手术组6只,缺血组15只,辛伐他汀干预组15只。干预组大鼠在模型制备前用辛伐他汀20mg/kg连续灌胃3d,1次/d;假手术组及缺血组用相同体积的等渗盐水连续灌胃3d。采用线栓法制备大鼠局灶性脑缺血-再灌注损伤模型,缺血2h,再灌注4h。采用硝酸盐比色法检测诱导型一氧化氮合酶(iNOS)活性、NO含量;2,3,5-氯化三苯基四氮唑(TTC)染色测定梗死体积;TUNEL染色法检测细胞凋亡情况。结果缺血-再灌注后干预组、缺血组及假手术组血清中NO含量分别为(89.3±3.0)、(124.9±4.6)、(66.5±3.1)μmol/L;iNOS活性分别为(15.8±2.7)、(23.0±2.9)、(11.1±2.5)U/ml;与缺血组比较,辛伐他汀干预能减少NO的含量,降低iNOS的活性(均P<0.01)。缺血组及干预组凋亡细胞数分别为(18.8±3.6)、(13.0±2.9)个/高倍视野,梗死体积分别为(160±10)、(135±11)mm3。结论辛伐他汀干预能减少脑缺血-再灌注损伤大鼠梗死体积及神经细胞凋亡。其机制可能是通过抑制iNOS的活性,降低NO的含量,从而起到神经保护作用。

Objective To discuss the protective effect of simvastatin on neurons following focal cerebral ischemia-reperfusion in rats and its mechanism. Methods Thirty-six rats were randomly allocated into sham-operation （ n = 6）, cerebral ischemia （ n = 15 ） and simvastatin intervention （ n = 15 ） groups. Before making a model, the rats in the intervention group were lavaged with simvastatin 20 mg/kg, once a day for 3 consecutive days, and the same volume of normal saline was lavaged for 3 consecutive days in the sham-operation and cerebral ischemia groups. The model of focal cerebral ischemia-reperfusion injury was induced by suture mothod （ iscbemia for 2 hours, and reperfusion for 4 hours ）. The activity of inducible nitric oxide synthase （iNOS） and the content of NO were detected by colorimetric method; cerebral infarction volume was determined by 2,3,5-triphenyltetrazolium chloride （TTC）, and cell apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling （TUNEL） staining method. Results After focal cerebral ischemia-reperfusion, the content of No in the simvastatin intervention, cerebral ischemia and sham-operation groups were 89. 3 ±3.0, 124. 9 ±4. 6 and 66. 5 ±3. 1 μmol/L, respectively; the activity of iNOS in these groups were 15. 8 ± 2.7, 23.0 ± 2. 9 and 11.1 ± 2. 5U/mL, respectively. Simvastatin intervention could reduce the content of No and the activity of iNOS as compared with the cerebral ischemia group （all P 〈0. 01 ）. The numbers of apeptotic cells in the cerebral ischemia and simvastatin intervention groups were 18.8 ± 3.6 and 13.0 ± 2. 9/high-power field, respectively, and their cerebral infarction volume was 160 10 and 135 11 mm^3, respectively. Conclusion Simvastatin intervention can reduce the volume of focal cerebral iscbemia-reperfusion injury in rats and the neuronal apoptosis. Its mechanism may be to due decrease the content of NO by inhibiting the activity of iNOS and playing a role of neuroprotection.