摘要
目的探索钙离子拮抗剂(CCB)和干预S100钙结合蛋白A4(S100A4)表达对SD大鼠下肢动脉硬化性闭塞症(ASO)动物模型发病进程的影响。方法将56只健康SD大鼠采用随机数字表分组法等分为8组, 每组7只。A组为对照组, B组为假手术组, C、D、E、F、G、H组则为通过采用手术联合高脂饮食的方式构建大鼠经典ASO模型后, 鼠尾静脉注射CCB、Lv-S100A4、S100A4小干扰RNA(siRNA)。通过茜素红染色评估股动脉中Ca2+浓度的改变, 苏木精-伊红(HE)染色评估股动脉内膜、中膜增生情况, 免疫组织化学检测股动脉S100A4的蛋白表达。计量资料两组间比较用独立样本t检验;多组间比较用单因素方差分析。计数资料采用χ2检验。等级资料采用秩和检验。结果 16周后成功构建大鼠ASO模型。F组中S100A4的表达显著低于E组(0.24±0.03比0.42±0.05, t=-6.774, P<0.01)且F组股动脉内膜及中膜厚度明显低于E组[(82.98±4.76) μm比(101.26±3.18) μm, t=-8.451, P<0.01]。H组中S100A4的表达显著低于G组(0.06±0.02比0.16±0.05, t=-4.502, P<0.01)且H组股动脉内膜及中膜厚度明显低于G组[(60.42±3.56) μm比(78.64±3.51) μm, t=-9.643, P<0.01]。结论 CCB可通过抑制Ca2+/S100A4信号通路进而影响动脉内膜及中膜增生过程, 达到减缓ASO病变进程的目的。
Objective To explore the effect of calcium channel blocker(CCB)and intervention in S100 calcium-binding protein A4(S100A4)expression on the pathogenesis of lower extremity arteriosclerosis obliterans(ASO)in SD rats.Methods The total 56 healthy SD rats were divided into 8 groups by a random number table grouping method,7 rats in each group.Group A was control group,group B was sham group.The classical ASO model of rats in groups C,D,E,F,G and H was established by surgery combined with high-fat diet.CCB,Lv-S100A4 and S100A4 small interfering RNA(siRNA)were respectively injected via the tail vein.Rats in each group were sacrificed 16 weeks later to harvest the femoral arteries.The changes of Ca2+concentration and the proliferation of the intima and media as well as the protein expression of S100A4 in the harvested femoral arteries were evaluated by alizarin red staining,hematoxylin and eosin(HE)staining and immunohistochemistry,respectively.Independent sample t-test was used for comparison between two groups.One-way ANOVA was used for comparisons among multiple groups.Chi-square test was used for the counting data analysis,and the rank sum test was employed for the rank data analysis.Results The rat ASO model was successfully established.As compared with group E,the expression of S100A4 in group F was significantly decreased(0.24±0.03 vs.0.42±0.05,t=-6.774,P<0.01)and the intima-media thickness of the femoral arteries was significantly reduced[(82.98±4.76)μm vs.(101.26±3.18)μm,t=-8.451,P<0.01].The expression of S100A4 in the group H was significantly declined(0.06±0.02 vs.0.16±0.05,t=-4.502,P<0.01)and the intima-media thickness of femoral arteries was significantly reduced[(60.42±3.56)μm vs.(78.64±3.51)μm,t=-9.643,P<0.01]as compared with the group G.Conclusion CCB inhibited the hyperplasia process of arterial intima and media by suppressing the Ca2+/S100A4 signaling pathway,and finally slowed down the progression of ASO lesions.
作者
周彬彬
夏印
黄军杰
党源
林晨
王烈
赵虎
Zhou Binbin;Xia Yin;Huang Junjie;Dang Yuan;Lin Chen;Wang Lie;Zhao Hu(Department of General Surgery,Fuzong Clinical Medical College of Fujian Medical University,900th Hospital of the Joint Logistics Support Force,Fuzhou 350025,China;Department of Vascular Surgery,the Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine/Fujian Provincial People’s Hospital,Fuzhou 350004,China;College of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350025,China;Innovation Center for Cancer Research,Fujian Medical University Cancer Hospital,Fujian Cancer Hospital,Fuzhou 350014,China)
出处
《中华实验外科杂志》
CAS
北大核心
2023年第8期1542-1545,共4页
Chinese Journal of Experimental Surgery
基金
福建省自然科学基金(2020J011127)。
