吴茱萸碱调节SDF-1α/CXCR4信号通路对颅内动脉瘤血管平滑肌细胞增殖和凋亡的影响  

Impacts of evodiamine on proliferation and apoptosis of vascular smooth muscle cells in intracranial aneurysms by regulating the SDF-1α/CXCR4 signaling pathway

作　　者：饶重贤 胡姗姗 谭伟[2] 王军民[3] 金胜昔[4] 周游[4] RAO Chongxian;HU Shanshan;TAN Wei(Brain Center,Geriatric Hospital Affiliated to Wuhan University of Science and Technology,Hubei,Wuhan 430065,China;不详)

机构地区：[1]武汉科技大学附属老年病医院脑科中心,武汉市430065 [2]武汉科技大学附属老年病医院全科医学科,武汉市430065 [3]武汉大学人民医院神经外科 [4]武汉科技大学附属天佑医院神经外科

出　　处：《河北医药》2024年第8期1151-1155,共5页Hebei Medical Journal

基　　金：湖北省卫生健康委2021-2022年度中医药科研立项项目(编号:ZY2021M074)。

摘　　要：目的探究吴茱萸碱通过调节基质细胞衍生因子1α(SDF-1α)/CXC趋化因子受体4(CXCR4)信号通路对颅内动脉瘤(IA)血管平滑肌细胞(VSMCs)的增殖和凋亡的作用。方法24只小鼠随机分为对照组和IA组,每组12只。IA组通过定位手术注射弹性蛋白酶制造IA模型小鼠,然后通过HE染色观察动脉组织变化。随后将小鼠主动脉血管平滑肌细胞(MOVAS)先用MTT法检测吴茱萸碱浓度对细胞的活性影响,然后将MOVAS分为ctrl组、Model组(H_(2)O_(2)诱导损伤组)、低浓度吴茱萸碱组(0.50μmol/L)、高浓度吴茱萸碱组(1.00μmol/L)、高浓度吴茱萸碱+CTCE-0214组(1.00μmol/L吴茱萸碱+10 mg/kg SDF-1α/CXCR4激活剂)。CCK-8试剂盒检测细胞活性;流式细胞术检测细胞凋亡;Western blot检测SDF-1α、CXCR4、BAX、增殖细胞核抗原(PCNA)、平滑肌22α(SM22α)和平滑肌α肌动蛋白(α-SMA)的蛋白表达。结果与对照组正常动脉组织比较,IA组的IA组织出现明显的病理变化,损伤严重。在MOVAS细胞实验中,与ctrl组比较,Model组的细胞凋亡率、SDF-1α、CXCR4、BAX蛋白表达增加,而细胞存活率、PCNA、SM22α、α-SMA含量降低(P<0.05)。与Model组比较,低浓度吴茱萸碱组、高浓度吴茱萸碱组的细胞凋亡率、SDF-1α、CXCR4、BAX蛋白表达降低,而细胞存活率、PCNA、SM22α、α-SMA含量升高(P<0.05);与高浓度吴茱萸碱组比较,高浓度吴茱萸碱+CTCE-0214组细胞凋亡率、SDF-1α、CXCR4、BAX蛋白表达升高,而细胞存活率、PCNA、SM22α、α-SMA含量降低(P<0.05)。结论吴茱萸碱可能通过抑制SDF-1α/CXCR4信号通路进而抑制颅内动脉瘤血管平滑肌细胞的凋亡,促进其增殖。Objective To investigate the impacts of evodiamine on the proliferation and apoptosis of vascular smooth muscle cells(VSMCs)in intracranial aneurysms(IA)by regulating the stromal cell derived factor-1α(SDF-1α)/CXC chemokine receptor 4(CXCR4)signaling pathway.Methods Twenty four mice were randomly divided into control group and IA group.The IA model in mice was created by stereotactic injection of elastase,and the changes in the arterial tissue were observed by hematoxylin and eosin(H&E)staining.The effect of evodiamine at varying concentrations on the viability of mouse aortic vascular smooth muscle(MOVAS)cells was detected by MTT assay.Then,MOVAS cells were induced with blank control,H_(2)O_(2),low-dose evodiamine(0.50μmol/L),high-dose evodiamine(1.00μmol/L)and high-dose evodiamine+CTCE-0214(1.00μmol/L evodiamine+10mg/kg SDF-1α/CXCR4 activator).Cell viability and apoptosis were detected by CCK-8 assay and flow cytometry,respectively.Western blot was applied to detect the protein expressions of SDF-1α,CXCR4,BAX,proliferating cell nuclear antigen(PCNA),smooth muscle 22α(SM22α)andα-smooth muscle actin(α-SMA).Results Compared with mice of blank control,IA mice showed significant pathological changes in the IA tissues and severe damage.Compared with those of blank control,MOVAS cells induced with H 2O 2 presented significantly higher apoptotic rate and protein expressions of SDF-1α,CXCR4 and BAX,and significantly lower cell survival rate and protein expressions of PCNA,SM22α and α-SMA(P<0.05).Compared with those induced with H 2O 2,MOVAS cells induced with low,high-dose evodiamine presented significantly lower apoptotic rate and protein expressions of SDF-1α,CXCR4 and BAX,and significantly higher cell survival rate and protein expressions of PCNA,SM22αandα-SMA(P<0.05).Compared with those induced with high-dose evodiamine,MOVAS cells induced with high-dose evodiamine+CTCE-0214 presented significantly higher apoptotic rate and protein expressions of SDF-1α,CXCR4 and BAX,and significantly lower cell su

关 键 词：吴茱萸碱 基质细胞衍生因子1Α CXC趋化因子受体4 颅内动脉瘤 血管平滑肌细胞 增殖 凋亡 

分 类 号：R543.16[医药卫生—心血管疾病]