丙戊酸对大鼠胸主动脉瘤抑制作用及机制  

Inhibition of Valproic Acid on Rat Thoracic Aortic Aneurysm and Its Mechanism

作　　者：汤锐[1] 谷天祥[1] 师恩祎[1] 王春[1] 张光伟[1] 毛乃惠[1] 

机构地区：[1]中国医科大学附属第一医院心外科,沈阳110001

出　　处：《中国胸心血管外科临床杂志》2015年第6期578-584,共7页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：国家自然科学基金资助项目(81171175)~~

摘　　要：目的探索丙戊酸抑制炎性细胞及平滑肌细胞从而对大鼠主动脉瘤的抑制作用。方法应用猪胰弹性蛋白酶通过外膜浸泡方法构建大鼠胸主动脉瘤模型,分为生理盐水空白对照组(C组)、外膜浸泡猪胰弹性蛋白酶(PPE)组(P组)和外膜浸泡PPE+腹腔注射丙戊酸(VPA)组(PV组),PV组行腹腔注射VPA 200 mg/kg,连续7 d。三组动物应用血管超声检测血管内径,于术后14 d取材,观察动脉瘤血管大体形态并对标本行染色分析,并对白介素1(interleukin 1,IL-1)、白介素6(interleukin 6,IL-6)、平滑肌SM22α蛋白(smooth muscle 22 alpha,SM22α),基质金属蛋白酶类(matrix metallopeptidases,MMPs)如MMP-2、MMP-9等指标进行免疫组织化学分析及Western blot法检测蛋白的表达水平。结果血管超声检测提示PV组血管内径小于对照P组(P<0.05),HE染色及免疫组织化学染色显示P组细胞排列无序、间质紊乱,PV组弹性蛋白层保存较为完好,PV组IL-1、IL-6、MMP-2、MMP-9蛋白表达明显下降,SM22α蛋白表达上升。结论 VPA可以抑制动脉瘤炎性细胞及平滑肌细胞的表型转化,降低细胞增殖水平,减少基质金属蛋白酶的分泌,抑制大鼠胸主动脉瘤生长。Objective To explore the inhibition action of valproic acid to inflammatory cells and smooth muscle cells then to find out that valproic acid （VPA） can repress rat thoracic aortic aneurysm or not. Methods The model of rat thoracic aortic aneurysm was built through the method of soaking the adventitia of artery using porcine pancreatic elastase （PPE）, The rats were divided into three groups： a normal saline blank control group （a C group）, an adventitia soaked PPE group （a P group）, and adventitia soaked PPE plus intraperitoneal injection by injecting intraperitioneal VPA 200 mg/kg for seven days （a PV group）.The animals of the three groups were all using vascular ultrasound to detect blood vessel diameter. Animals were killed after operation to observe the general morphology of vascular aneuysm and do the immunohistochemial, morphological, protein analysis of interleukin 1 （IL-1） , interleukin 6 （IL-6） , smooth muscle 22 alpha （SM22a）, matrix metallopeptidase 2 （MMP-2）, MMP-9 and Western blot by drawing animals on the 14th day. Results The vessels diameter in the PV group was narrower than that in the P group （P value〈0.05）. HE staining, immunohistochemistry and Western blot displayed that the cells in the P group were in disorder arrangement and interstitial disorder while the cells in the PV group maintained better albumin layer. The protein expressions of IL-1, IL-6, MMP-2, and MMP-9 in the PV group decreased except that SM22ct increased. Conclusion VPA can inhibit phenothpic transforming of aneurysm inflammatory cells and smooth muscle cells, reduce the levels of cell proliferation, decrease the secretion of matrix metalloproteinases, and depress tumor growth of rat thoracic aorta.

关 键 词：丙戊酸 炎性细胞 平滑肌细胞 基质金属蛋白酶 

分 类 号：R543.16[医药卫生—心血管疾病]