机构地区:[1]沈阳医学院附属中心医院心血管内科,辽宁沈阳110024 [2]中国医科大学组织工程学教研室,辽宁沈阳110013
出 处:《中国新药与临床杂志》2019年第7期422-427,共6页Chinese Journal of New Drugs and Clinical Remedies
基 金:辽宁省科技厅课题(201705040869,201705040881);沈阳市科技局课题(17-230-9-32,17-230-9-70)
摘 要:目的观察酰基化和非酰基化胃饥饿素(ghrelin, Ghr)对大鼠颈动脉内膜损伤的作用并探讨相关机制。方法采用球囊损伤法建立颈动脉内膜损伤模型, 30只制模成功的雄性SD大鼠随机分为3组,每组10只,分别为模型组、酰基化Ghr (30 nmol·kg-1)组和非酰基化Ghr (30 nmol·kg-1)组,予高脂饲料;另随机选择10只健康雄性SD大鼠作为正常对照组,予正常饲料。各组均腹腔注射给药,每日1次,治疗4周后,采血检测血脂和C反应蛋白(CRP)水平, HE染色后测量损伤动脉厚度及内膜-中膜厚度比, Western blot法检测损伤动脉组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、胞间黏附分子-1 (ICAM-1)和血管细胞黏附分子-1 (VCAM-1)蛋白表达水平。结果与正常对照组比较,模型组大鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和CRP水平显著升高,高密度脂蛋白胆固醇(HDL-C)水平显著降低(P <0.05或P <0.01),颈动脉内膜显著增厚,内膜-中膜厚度比显著增加(P <0.01), TNF-α、 IL-1β、 ICAM-1和VCAM-1蛋白表达上调(P <0.05或P <0.01)。与模型组比较,酰基化Ghr组和非酰基化Ghr组大鼠血清TC、 LDL-C、 CRP水平显著降低, HDL-C水平显著升高(P <0.01),颈动脉内膜厚度显著减小、内膜-中膜厚度比显著降低(P <0.01), TNF-α、 IL-1β和ICAM-1蛋白表达降低(P <0.05或P <0.01)。酰基化Ghr组和非酰基化Ghr组各指标比较均无显著差异(P> 0.05)。结论酰基化和非酰基化Ghr均能通过调血脂、减轻炎症反应而缓解大鼠颈动脉内膜损伤,且两者作用无明显差异。AIM To study the effects of acylated and unacylated ghrelin(Ghr) on carotid intimal injury in rat and its mechanism. METHODS The model of carotid intimal injury was performed by balloon injury.Thirty male intimal injury model SD rats were randomly divided into 3 groups(10 rats in each group): model group, acylated Ghr( 30 nmol·kg-1) group and unacylated Ghr( 30 nmol·kg-1) group, given high fat diet.Another 10 healthy male SD rats were randomly selected as the normal control group with normal diet. All rats were administered intraperitoneally once a day. After 4 weeks after intervention, blood lipids and C-reactive protein( CRP) were measured. The thickness of damaged artery and intima-media thickness ratio were measured after HE staining. Western blot was used to detect the protein expression of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1( VCAM-1) in the carotid artery. RESULTS Compared with the control group, serum levels of total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG) and CRP levels in the model group were significantly increased, while high-density lipoprotein cholesterol( HDL-C) were decreased( P < 0.05 or P < 0.01). Carotid artery intima was significantly thickened, and the intima-media thickness ratio was significantly increased( P < 0.01). Compared with the model group, serum levels of TC,LDL-C and CRP in the acylated and unacylated Ghr groups decreased and HDL-C increased(P< 0.05 or P<0.01). Carotid intimal thickness decreased significantly, and the intimal-media thickness ratio decreased significantly(P < 0.01), and the expression of TNF-α, IL-1β, and ICAM-1 decreased(P< 0.05 or P< 0.01).There were no significant differences in all index between the acylated and unacylated Ghr groups( P >0.05).CONCLUSION Acylated and unacylated Ghr can alleviate the carotid intimal injury through blood lipid and inflammatory pathways, and there is no significant difference between the
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