前列地爾注射液通過抑制自噬減輕肺缺血再灌注損傷
本文選題:肺缺血再灌注損傷 + 前列地爾注射液 ; 參考:《山西醫(yī)科大學(xué)》2017年碩士論文
【摘要】:目的:探討大鼠肺組織缺血再灌注損傷時自噬水平的變化以及肺缺血再灌注損傷時前列地爾注射液的保護作用,進一步研究前列地爾注射液能否通過調(diào)節(jié)自噬減輕大鼠肺的缺血再灌注損傷(ischemia and reperfusion injury,IRI)。方法:健康成年雄性Wistar大鼠75只,采用開胸夾閉右肺門建立IRI模型,將75只Wistar大鼠編號后按隨機數(shù)字表法分為五組,分別為:對照組(Sham組)、缺血再灌注處理組(I/R組)、前列地爾注射液處理組(Alp組)、前列地爾注射液+自噬激活劑雷帕霉素(Rapamycin)處理組(Alp+Rap組)和Rapamycin處理組(Rap組),各15只。缺血60min,再灌注120min后處死大鼠。再灌注結(jié)束后經(jīng)胸主動脈取動脈血測定動脈血氧飽和度(PaO2);大鼠處死后取部分右肺,稱濕重、干重,計算濕干重比(W/D),石蠟包埋剩余肺組織,并切片,蘇木精-伊紅(HE)染色后電鏡觀察肺組織病理變化,計算其肺損傷病理學(xué)評分;另免疫熒光雙染色法觀察自噬相關(guān)蛋白LC3、Beclin-1的染色情況。結(jié)果:與Sham組相比,I/R組PaO2明顯降低,W/D值明顯增大,肺損傷程度明顯加重,LC3、Beclin-1蛋白表達水平明顯上升(P㩳0.05)。與I/R組比較,Alp組PaO2值顯著增大,W/D值顯著減小,肺組織損傷程度顯著減輕,LC3、Beclin-1蛋白表達水平明顯下降(P㩳0.05)。Rapamycin能削弱前列地爾注射液的作用。結(jié)論:肺缺血再灌注損傷時自噬水平升高,前列地爾注射液可減輕大鼠肺組織肺缺血再灌注損傷,且與自噬有關(guān),激活自噬則可以加重肺的缺血再灌注損傷。
[Abstract]:Objective: to investigate the changes of autophagy level in lung tissue of rats with ischemia-reperfusion injury and the protective effect of alprostadil injection on lung ischemia-reperfusion injury. To further study whether alprostadil injection can alleviate and reperfusion injury by regulating autophagy in rats. Methods: 75 healthy adult male Wistar rats were used to establish IRI model by opening the right lung hilum. The 75 Wistar rats were numbered and randomly divided into five groups. The results were as follows: control group (Sham group), ischemia-reperfusion group (I / R group), alprostadil injection group (Alp group), alprostadil injection autophagy activator rapamycin (rapamycin) treatment group (Alp Rap group) and Rapamycin treatment group (Rap group, 15 rats each). Rats were killed after ischemia for 60 minutes and reperfusion for 120min. After reperfusion, arterial blood was taken from the thoracic aorta to determine the arterial oxygen saturation. After the rats were killed, part of the right lung was taken to weigh wet weight and dry weight, the wet / dry weight ratio was calculated, and the remaining lung tissue was embedded in paraffin and sectioned. The pathological changes of lung tissue were observed by electron microscope after hematoxylin and eosin HEV staining, and the pathological scores of lung injury were calculated, and the staining of autophagy associated protein LC3 / Beclin-1 was observed by double immunofluorescence staining. Results: compared with the Sham group, the PaO2 decreased significantly in the I / R group and the W / D value increased significantly, and the expression level of Beclin-1 protein increased significantly in the lung injury group (P < 0.05). Compared with the I / R group, the PaO2 value of Alp group increased significantly and the W / D value decreased significantly, and the degree of lung injury significantly reduced the expression level of LC3 / Beclin-1 protein. Rapamycin could weaken the effect of proprostadil injection. Conclusion: the level of autophagy increased during lung ischemia-reperfusion injury. Alprostadil injection can attenuate lung ischemia-reperfusion injury in rats and is related to autophagy. Activation of autophagy can aggravate the ischemia-reperfusion injury of lung.
【學(xué)位授予單位】:山西醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R563
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