本文選題：肺動脈高壓 + 早期纖維化　； 參考：《南京醫(yī)科大學(xué)學(xué)報(自然科學(xué)版)》2017年09期

【摘要】：目的:探討琥珀酸能否促進野百合堿誘導(dǎo)的肺動脈高壓大鼠模型心肺小動脈間質(zhì)纖維化,并初步探索其機制。方法:4~5周齡健康雄性SD大鼠30只,體重120~180 g,隨機分為對照組、野百合堿(monocrotaline,MCT)組、野百合堿和琥珀酸(succinic acid,SUC)聯(lián)合使用組(MCT+SUC組),每組10只。MCT組和MCT+SUC組予腹腔注射MCT建造大鼠肺小動脈高壓模型,MCT+SUC組繼續(xù)予SUC干預(yù)4周。4周后,利用漂浮導(dǎo)管檢測平均肺動脈壓(mean pressure of pulmonary artery,mPAP)、右心室收縮壓(right ventricular systolic pressure,RVSP)、肺動脈收縮壓(systolic blood pressure,SBP)和肺動脈舒張壓(diastolic blood pressure,DBP)等血流動力學(xué)指標(biāo)。安樂死后取組織測定右室肥厚指數(shù),行HE染色觀察心臟和肺組織小動脈的肌化情況,Masson、天狼星紅染色觀測心臟和肺小動脈周圍纖維化情況,Western blot和免疫組織化學(xué)檢測心臟組織血管緊張素Ⅱ(angiotensinⅡ,AngⅡ)、血小板衍生因子-BB(platelet derived growth factor,PDGF-BB)和成纖維細胞生長因子-2((fibroblast growth factor 2,FGF2)等蛋白表達水平。結(jié)果:MCT組、MCT+SUC組大鼠均表現(xiàn)食量減少、倦臥等癥狀,MCT+SUC組大鼠出現(xiàn)唇周紫紺、氣促等表現(xiàn)較早。MCT+SUC組RVSP、mPAP、肺動脈SBP和肺動脈DBP、右室肥厚指數(shù)、心肺小動脈中層增厚程度均明顯大于MCT組(P均0.05)。HE染色顯示,MCT組心肺小動脈輕度增厚,MCT+SUC組心臟小動脈壁增厚程度較MCT組更加明顯,局部心肌組織炎性細胞浸潤增加。天狼星紅染色與Masson染色結(jié)果顯示,MCT+SUC組心肺小動脈周圍間質(zhì)內(nèi)膠原纖維異常增生,MCT組心肺小動脈周圍未見膠原纖維異常增生。Western blot和免疫組織化學(xué)結(jié)果顯示,MCT+SUC組和MCT組肺組織AngⅡ、PDGF-BB、FGF2蛋白表達水平變化與對照組相比均有不同程度的升高,MCT+SUC組較MCT組上升水平更加明顯。結(jié)論:SUC可以促進MCT誘導(dǎo)的心肺小動脈間質(zhì)纖維化的形成,其機制可能是上調(diào)FGF2和PDGF-BB等促纖維化的細胞因子,AngⅡ表達升高,導(dǎo)致心肺小動脈間質(zhì)纖維化的形成。
[Abstract]:Aim: to investigate whether succinic acid can promote the interstitial fibrosis of pulmonary arterioles induced by monocrotaline in rats with pulmonary hypertension and to explore its mechanism. Methods Thirty healthy male Sprague-Dawley rats of 5 weeks old, weighing 120,180 g, were randomly divided into control group and monocrotaline monocrotaline (MCTT) group. Monocrotaline and succinic acidosis suc) were used in each group with 10 rats in each group. MCT group and MCT SUC group were given intraperitoneal injection of MCT to construct pulmonary arteriolar hypertension in rats. The SUC group was treated with SUC for 4 weeks. The mean pressure of pulmonary arterial pressure (mean pressure of pulmonary), right ventricular systolic pressure (RVSPV), systolic blood pressure (SBP) and pulmonary diastolic blood pressure (DBP) were measured by floating catheter. The right ventricular hypertrophy index was measured after euthanasia. He staining was used to observe the muscularization of the arterioles in heart and lung tissue, Sirius red staining was used to observe the fibrosis around the heart and pulmonary arterioles, and immunohistochemistry was used to detect angiotensin 鈪，

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