摘要
目的观察粒细胞集落刺激因子(G-CSF)对大鼠颈总动脉球囊损伤后内皮修复的作用及钙敏感受体(CaSR)相关机制。方法SD大鼠30只,随机均分为假手术组、模型组和G-CSF组。制备左侧颈总动脉球囊损伤模型。术后G-CSF组皮下注射G-CSF 30μg·kg^-1·d^-1,连续7 d,假手术组和模型组给予等量生理盐水,于第14日麻醉动物后取球囊损伤处颈总动脉,HE染色后观察血管再狭窄情况,免疫组化法检测CD31、CaSR、JNK、P38蛋白表达;免疫荧光双标法检测CD133、α-平滑肌激动蛋白(α-SMA)的表达。结果与假手术组相比,模型组大鼠颈总动脉损伤处新生内膜面积(NIA)显著增加,NIA-中膜面积(MA)比增加,NIA-内弹力板围绕面积(IELA)比增加,管腔面积(LA)减少(P<0.05或P<0.01),CaSR、JNK、P38蛋白的阳性表达增加,CD133、α-SMA双阳性分布增加(P<0.05)。与模型组比较,G-CSF组NIA、NIA/MA、NIA/IELA均降低,而LA增大(P<0.01);血管损伤部位CD31表达增加(P<0.05),CaSR、JNK、P38蛋白的阳性表达降低(P<0.05),CD133和α-SMA的双阳性分布降低(P<0.05)。结论G-CSF促进大鼠颈总动脉球囊损伤后内皮修复,抑制内膜增生,其机制可能与CaSR有关。
AIM To observe the effect of granulocyte colony stimulating factor(G-CSF)on endothelial repair after carotid artery balloon injury in rats and the mechanism of calcium sensing receptor(CaSR).METHODS Thirty SD rats were randomly divided into sham group,model group and G-CSF group,10 in each group.The rat model was established by left common carotid artery balloon injury.The G-CSF group were injected subcutaneously with G-CSF 30μg·kg-1·d-1 for 7 days.The sham and model group were given equivalent saline.The left common carotid arteries were taken 14 days late.After HE staining,the vascular restenosis was observed.The protein expressions of CD31,CaSR,JNK and P38 were detected by immunohistochemistry.The expression of CD133 and alpha smooth muscle actin(α-SMA)in vascular tissue were detected by double immunofluorescence staining.RESULTS Compared with the sham group,the area of neointima(NIA)increased,the area of neointima(NIA)/media area(MA)and NIA/elastic area(IELA)ratio also increased,lumen area(LA)decreased in the model group(P<0.05 or P<0.01).Moreover the positive expression of CaSR,JNK and P38 protein increased,and the double positive distribution of CD133 andα-SMA increased(P<0.05).Compared with the model group,NIA,NIA/MA and NIA/IELA decreased while LA increased(P<0.01),the expression of CD31 increased in vascular lesion(P<0.05).The double positive distribution of CD133 andα-SMA decreased,while the positive expression of CaSR and downstream JNK and P38 protein decreased in the G-CSF group(P<0.05).CONCLUSION G-CSF promotes endothelial repair after balloon injury of common carotid artery in rats,inhibits intimal hyperplasia and prevents restenosis.The mechanism may be related to CaSR.
作者
徐尚福
向志伟
胡安玲
帅芝琴
贾为壹
黄波
李利生
XU Shang-fu;XIANG Zhi-wei;HUAn-ling;SHUAI Zhi-qin;JIA Wei-yi;HUANG Bo;LI Li-sheng(Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education,Zunyi Medical University,Zun/yi GUIZHOU 563003,China;Research Center for Medicine&Biology,Zunyi Medical University,Zun/yi GUIZHOU 563003,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2020年第3期175-180,共6页
Chinese Journal of New Drugs and Clinical Remedies
基金
国家自然科学基金项目(81560592)
贵州省科学技术基金项目(黔科合J字[2011]2318号)
贵州省中医药管理局科学技术项目(QZYY2011-66)。
关键词
粒细胞集落刺激因子
钙敏感受体
再狭窄
granulocyte colony stimulating factor
calcium sensing receptor
restenosis