本文關(guān)鍵詞： 動(dòng)脈粥樣硬化 肝細(xì)胞生長因子 間質(zhì)-上皮轉(zhuǎn)化因子 炎癥因子 M1型巨噬細(xì)胞 M2型巨噬細(xì)胞　出處：《安徽醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的通過對(duì)動(dòng)脈粥樣硬化(AS)模型兔多次肌肉注射重組腺病毒-肝細(xì)胞生長因子(Ad-HGF),探討肝細(xì)胞生長因子(HGF)對(duì)AS模型兔巨噬細(xì)胞M1型標(biāo)志物精氨酸酶II(Arg II)及誘導(dǎo)性一氧化氮合酶(i NOS)的表達(dá)、巨噬細(xì)胞M2型標(biāo)志物CD163及精氨酸酶I(Arg I)的表達(dá)、血清炎癥因子、血脂和AS斑塊成分的影響。方法40只4月齡雄性新西蘭大耳兔隨機(jī)分為正常組、AS模型組、空載體腺病毒(null-Ad)組,Ad-HGF組,正常組給予普通飼料,其余各組均給予高膽固醇飼料。于喂養(yǎng)第4周、5周、6周時(shí),Ad-HGF組肌肉注射1 ml Ad-HGF(5×109PFU/m L·只),null-Ad組肌肉注射1 ml null-Ad(5×109PFU/m L·只),正常組和AS模型組注射等量生理鹽水。12周留取血液標(biāo)本后處死動(dòng)物取出主動(dòng)脈,分別測定血清炎癥因子IL-6、IL-10、血脂水平,主動(dòng)脈內(nèi)膜/中膜厚度比值(IMT),血管平滑肌細(xì)胞(VSMCs)、膠原纖維和巨噬細(xì)胞的含量,主動(dòng)脈HGF、間質(zhì)-上皮轉(zhuǎn)化因子(c-Met)、Arg-II、i NOS、CD163、Arg I的蛋白表達(dá)。結(jié)果與正常組比較,AS模型組血清IL-6、血脂水平、主動(dòng)脈Arg II、i NOS的蛋白表達(dá)、IMT、膠原纖維及巨噬細(xì)胞含量明顯增加(P0.05),血清IL-10水平、主動(dòng)脈HGF、c-Met、CD163、Arg I的蛋白表達(dá)、VSMCs含量明顯降低(P0.05);與AS模型組相比,null-Ad組血清炎癥因子IL-6、IL-10、血脂水平,IMT,VSMCs、膠原纖維和巨噬細(xì)胞的含量,主動(dòng)脈HGF、c-Met、Arg II、i NOS、CD163、Arg I的蛋白表達(dá)無明顯差別(P0.05);與AS模型組相比,Ad-HGF組血脂水平無明顯差別(P0.05),血清IL-6水平、主動(dòng)脈Arg II、i NOS的蛋白表達(dá)、IMT及巨噬細(xì)胞含量明顯降低(P0.05),血清IL-10水平、主動(dòng)脈HGF、c-Met、CD163、Arg I的蛋白表達(dá)、VSMCs含量、膠原纖維含量明顯增加(P0.05)。結(jié)論HGF降低AS模型兔促炎因子水平,增加抗炎因子水平,抑制M1型巨噬細(xì)胞浸潤、誘導(dǎo)M2型巨噬細(xì)胞分化、增加斑塊VSMCs和膠原纖維含量而促進(jìn)斑塊穩(wěn)定、抑制AS進(jìn)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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R543.5

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