CAJ | 학술논문

目的观察阿托伐他汀对局灶性脑缺血大鼠脑组织血管新生的影响并探讨相应机制.方法选用雄性SD大鼠90只,按照随机数字表法分为假手术组、模型组、治疗组,每组再分为3个亚组:1d组、3d组、7d组,每亚组10只.模型组及治疗组大鼠按照大脑中动脉栓塞法制备局灶性脑缺血模型,假手术组只分离血管,不结扎,不插线.建模后3h,治疗组给予阿托伐他汀钙片4 mg/(kg·d)灌胃,其余2组在相应时间给予等量生理盐水灌胃.大鼠建模后3h及给药后1d、3d、7d给予神经功能评分;同时间点采用免疫组化染色法检测新生血管内皮细胞标志物CD105、葡萄糖调节蛋白78(GRP78);RT-PCR检测血管内皮细胞生长因子(VEGF) mRNA;Western blotting检测凋亡蛋白Caspase-12.结果 (1)模型组和治疗组大鼠建模后3h神经功能评分差异无统计学意义(P＞0.05),其余时间点评分差异均有统计学意义(P＜0.05).(2)各时间点模型组大鼠微血管密度均较假手术组大鼠增加,治疗组大鼠均较模型组大鼠增加,差异均有统计学意义(P＜0.05).(3)VEGFmRNA表达随时间延长逐渐升高;各时间点模型组大鼠均较假手术组大鼠表达增加,治疗组大鼠均较模型组大鼠表达增加,差异有统计学意义(P＜0.05).(4) GRP78、Caspase-12表达随时间延长逐渐降低;各时间点模型组大鼠均较假手术组大鼠表达增加,治疗组大鼠均较模型组大鼠表达降低、较假手术组表达增加,差异有统计学意义(P＜0.05).结论局灶性脑缺血大鼠脑组织血管新生明显,且阿托伐他汀可增强此效应,其机制可能为减弱内质网应激,减少内皮细胞凋亡.
목적 관찰아탁벌타정대국조성뇌결혈대서뇌조직혈관신생적영향병탐토상응궤제.방법 선용웅성SD대서90지,안조수궤수자표법분위가수술조、모형조、치료조,매조재분위3개아조:1d조、3d조、7d조,매아조10지.모형조급치료조대서안조대뇌중동맥전새법제비국조성뇌결혈모형,가수술조지분리혈관,불결찰,불삽선.건모후3h,치료조급여아탁벌타정개편4 mg/(kg·d)관위,기여2조재상응시간급여등량생리염수관위.대서건모후3h급급약후1d、3d、7d급여신경공능평분;동시간점채용면역조화염색법검측신생혈관내피세포표지물CD105、포도당조절단백78(GRP78);RT-PCR검측혈관내피세포생장인자(VEGF) mRNA;Western blotting검측조망단백Caspase-12.결과 (1)모형조화치료조대서건모후3h신경공능평분차이무통계학의의(P＞0.05),기여시간점평분차이균유통계학의의(P＜0.05).(2)각시간점모형조대서미혈관밀도균교가수술조대서증가,치료조대서균교모형조대서증가,차이균유통계학의의(P＜0.05).(3)VEGFmRNA표체수시간연장축점승고;각시간점모형조대서균교가수술조대서표체증가,치료조대서균교모형조대서표체증가,차이유통계학의의(P＜0.05).(4) GRP78、Caspase-12표체수시간연장축점강저;각시간점모형조대서균교가수술조대서표체증가,치료조대서균교모형조대서표체강저、교가수술조표체증가,차이유통계학의의(P＜0.05).결론 국조성뇌결혈대서뇌조직혈관신생명현,차아탁벌타정가증강차효응,기궤제가능위감약내질망응격,감소내피세포조망.
Objective To investigate the effect ofatorvastatin on angiogenesis of brain tissues in focal cerebral ischemia rats,and explore the corresponding mechanism.Methods Ninety male SD rats were randomly divided into sham-operated group,model group and treatment group (n=30);and then,each group was divided into three subgroups:1 d group,3 d group and 7 d group (n=10).The focal cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO);3 h after MCAO,rats in the treatment group received a gavage of atorvastatin 4 mg/(kg.d),and others were given the same amount of normal saline at corresponding time.The nerve function defects were estimated at 3 h after MCAO and before being killed;the protein expressions of vascular endothelial cell markers CD105 and glucose-regulated protein 78 (GRP78) were analyzed by immunohistochemistry;the vascular endothelial growth factor (VEGF) mRNA expression was analyzed by real time-PCR;the caspase-12 protein expression was analyzed by Western blotting.Results (1) Nerve function defects scores:there was no significantly statistical difference between model group and treatment group at 3 h after MCAO (P＞0.05),but statistical differences at different time points before being killed were noted (P＜0.05).(2) Microvessel density (MVD):at all time points,that of model group was increased as compared with that of sham-operated group,that of treatment group was increased as compared with that of model group,and the differences were all statistically significant (P＜0.05).(3)The VEGF rmRNA expression gradually increased over time;at all time points,the VEGF mRNA expression of model group was significantly higher than that in the sham-operated group,and that of treatment group was significantly higher than that in the model group (P＜0.05).(4)The GRP78 and caspase-12 expressions were gradually decreased over time;at all time points,the GRP78/BiP and caspase-12 expressions in the model group were significantly higher than those in the sham-operated group;those in the treatment group were statistically lower than those in the model group,but obviously higher than those in the sham-operated group (P＜0.05).Conclusion The angiogenesis of brain tissues in MCAO rats is obvious,and atorvastatin can enhance this effect;the mechanism may be that atorvastatin can weaken the endoplasmic reticulum stress,and then,reduce the apoptosis of endothelial cells.