肝细胞生长因子对动脉粥样硬化模型兔巨噬细胞M1、M2亚型及斑块成分的影响

发布时间：2018-02-05 21:40

本文关键词： 动脉粥样硬化肝细胞生长因子间质-上皮转化因子炎症因子 M1型巨噬细胞 M2型巨噬细胞　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的通过对动脉粥样硬化(AS)模型兔多次肌肉注射重组腺病毒-肝细胞生长因子(Ad-HGF),探讨肝细胞生长因子(HGF)对AS模型兔巨噬细胞M1型标志物精氨酸酶II(Arg II)及诱导性一氧化氮合酶(i NOS)的表达、巨噬细胞M2型标志物CD163及精氨酸酶I(Arg I)的表达、血清炎症因子、血脂和AS斑块成分的影响。方法40只4月龄雄性新西兰大耳兔随机分为正常组、AS模型组、空载体腺病毒(null-Ad)组,Ad-HGF组,正常组给予普通饲料,其余各组均给予高胆固醇饲料。于喂养第4周、5周、6周时,Ad-HGF组肌肉注射1 ml Ad-HGF(5×109PFU/m L·只),null-Ad组肌肉注射1 ml null-Ad(5×109PFU/m L·只),正常组和AS模型组注射等量生理盐水。12周留取血液标本后处死动物取出主动脉,分别测定血清炎症因子IL-6、IL-10、血脂水平,主动脉内膜/中膜厚度比值(IMT),血管平滑肌细胞(VSMCs)、胶原纤维和巨噬细胞的含量,主动脉HGF、间质-上皮转化因子(c-Met)、Arg-II、i NOS、CD163、Arg I的蛋白表达。结果与正常组比较,AS模型组血清IL-6、血脂水平、主动脉Arg II、i NOS的蛋白表达、IMT、胶原纤维及巨噬细胞含量明显增加(P0.05),血清IL-10水平、主动脉HGF、c-Met、CD163、Arg I的蛋白表达、VSMCs含量明显降低(P0.05);与AS模型组相比,null-Ad组血清炎症因子IL-6、IL-10、血脂水平,IMT,VSMCs、胶原纤维和巨噬细胞的含量,主动脉HGF、c-Met、Arg II、i NOS、CD163、Arg I的蛋白表达无明显差别(P0.05);与AS模型组相比,Ad-HGF组血脂水平无明显差别(P0.05),血清IL-6水平、主动脉Arg II、i NOS的蛋白表达、IMT及巨噬细胞含量明显降低(P0.05),血清IL-10水平、主动脉HGF、c-Met、CD163、Arg I的蛋白表达、VSMCs含量、胶原纤维含量明显增加(P0.05)。结论HGF降低AS模型兔促炎因子水平,增加抗炎因子水平,抑制M1型巨噬细胞浸润、诱导M2型巨噬细胞分化、增加斑块VSMCs和胶原纤维含量而促进斑块稳定、抑制AS进展。
[Abstract]:Objective to intramuscularly inject recombinant adenovirus-hepatocyte growth factor (HGF) into the atherosclerotic atherosclerotic model rabbits. To investigate the expression of hepatocyte growth factor (HGF) on argininase type 1 (II(Arg II) and inducible nitric oxide synthase (iNOS) in macrophages of as model rabbits. Expression of macrophage M2 marker CD163 and argininase Ig Arg I, serum inflammatory factors. Methods Forty 4-month-old male New Zealand rabbits were randomly divided into normal as model group and empty vector adenovirus null-Ad-Ad-HGF group. The normal group was given normal diet and the other groups were given high cholesterol diet. Ad-HGF group was intramuscularly injected with 1 ml Ad-HGF(5 脳 109 PFU / mL 路mouse. Null-Ad group was intramuscularly injected with 1 ml null-Ad(5 脳 109 PFU / mL 路mouse. The normal group and as model group were injected with the same amount of normal saline for 12 weeks, then the rats were sacrificed to take out the aorta, and the serum levels of IL-6, IL-10 and lipids were measured respectively. The ratio of intima-media thickness to intima-media thickness of aorta (IMT), vascular smooth muscle cell (VSMC), collagen fiber and macrophage content, aortic HGF, interstitial epithelium transforming factor c-Metals. Results compared with the normal group, the level of serum IL-6, serum lipids and aortic Arg II in the as model group were higher than those in the control group. The protein expression of I NOS, the content of collagen fiber and macrophage were significantly increased (P 0.05), the level of serum IL-10 and aortic HGF c-Mett CD163 were also significantly increased. The protein expression of Arg I significantly decreased the content of P0.05C. Compared with as model group, the levels of serum inflammatory factor IL-6 and IL-10, serum lipids level and the contents of collagen fibers and macrophages, HGF of aorta were measured in null-Ad group. There was no significant difference in the protein expression of c-Meta Arg II-NOSU CD163 and Arg I between the two groups (P 0.05). Compared with as model group, there was no significant difference in blood lipid level, serum IL-6 level and protein expression of aortic Arg III NOS in Ad-HGF group. The content of IMT and macrophage decreased significantly, the level of serum IL-10 and the protein expression of aorta HGFC-MetCD163 / Arg I were significantly decreased. Conclusion HGF can decrease the level of proinflammatory factor, increase the level of anti-inflammatory factor, inhibit the infiltration of M1 macrophage and induce the differentiation of M2 macrophage. Increased plaque VSMCs and collagen fibers increased plaque stability and inhibited as progression.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R543.5

【参考文献】