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目的观察兔蛛网膜下腔出血(subarachnoid hemorrhage,SAH)模型基底动脉小窝蛋白-1(Caveolin-1)和血小板源性生长因子(platelet-derived growth factor,PDGF)随时间表达变化情况,分析caveolin-1与动脉中膜平滑肌细胞增殖的关系。方法采用随机数字表法将76只新西兰大白兔完全随机分为空白对照组、假手术组和SAH组,空白组(各8只)不施加任何因素干扰,SAH组通过枕大池2次注血模拟脑血管痉挛病理过程,假手术组以生理盐水代替自体动脉血。于2次注血完毕后第1、3、5、7、14天取材,进行基底动脉组织学观察;RT-PCR、Western blot检测caveolin-1及PDGF mRNA转录及蛋白表达的变化规律。结果 SAH组基底动脉中膜滑肌层第7天增厚最为明显(39.92±4.07)μm,较sham组(10.78±2.14)μm显著增厚(P<0.01),第14天恢复正常;SAH组caveolin-1 mRNA转录水平上调,第5天达峰(63.41±4.47)%,较sham组(11.75±1.84)%显著上调(P<0.01),蛋白表达则持续下降,第7天(13.78±0.59)%较sham组(37.63±0.85)%显著下调(P<0.01);SAH组PDGF mRNA转录水平第3天(64.45±4.00)%较sham组(11.13±1.20)%显著上调(P<0.01),蛋白表达于第7天达峰(40.67±0.81)%,较sham组(15.42±1.00)%显著上调(P<0.01);Cavelin-1蛋白表达与基底动脉中膜平滑肌层厚度呈显著负相关(r=-0.89,P<0.01)。结论 Caveolin-1蛋白在SAH后脑血管平滑肌细胞增殖过程中持续下调,可能是抑制血管痉挛平滑肌增殖反应的潜在靶点。
Objective To observe the changes of caveolin-1 and platelet-derived growth factor (PDGF) expression in subarachnoid hemorrhage (SAH) -1 and Arterial Membrane Smooth Muscle Cell Proliferation. Methods Sixty-six New Zealand white rabbits were randomly divided into blank control group, sham operation group, SAH group and blank control group (8 rats in each group) without any interference. SAH group Cerebral vasospasm pathological process, sham operation group instead of autologous arterial blood. The basal arteries were observed on the 1st, 3rd, 5th, 7th and 14th day after the second injection. The transcription and protein expression of caveolin-1 and PDGF were detected by RT-PCR and Western blot. Results In the SAH group, the basilar artery intima-media thickness was the most obvious on day 7 (39.92 ± 4.07 μm), significantly thicker than that in sham group (10.78 ± 2.14) μm (P <0.01), and returned to normal on the 14th day. The mRNA level of caveolin-1 was up-regulated on the fifth day (63.41 ± 4.47)%, significantly higher than that of the sham group (11.75 ± 1.84)% (P <0.01) )% Was significantly lower than sham group (37.63 ± 0.85)% (P <0.01). The level of PDGF mRNA transcription in SAH group was significantly higher than that in sham group at day 3 (64.45 ± 4.00)% (11.13 ± 1.20)% (40.67 ± 0.81)% on the 7th day, which was significantly higher than that of sham group (15.42 ± 1.00)% (P <0.01). The protein expression of Cavelin-1 was negatively correlated with the thickness of tunica media in basilar artery (r = -0.89, P <0.01). Conclusions The down-regulation of Caveolin-1 protein in the proliferation of cerebrovascular smooth muscle cells after SAH may be a potential target for inhibiting the proliferation of vascular smooth muscle cells induced by vasospasm.