本文選題：危重癥胰腺炎 + p-gsk-3β　； 參考：《河北聯(lián)合大學(xué)》2014年碩士論文

【摘要】：目的急危重癥胰腺炎（SAP）并發(fā)心臟損害的死亡率極高，嚴(yán)重威脅患者的生命。通過分子生物學(xué)手段探討其發(fā)生的具體機(jī)制，并為開發(fā)合理的臨床用藥提供理論依據(jù)。 方法本研究利用5%的�；悄懰徕c建立大鼠SAP模型，將80只健康雄性SD大鼠隨機(jī)分為兩組，假手術(shù)組（sham組）及模型組，每組各40只，每組又下設(shè)0h、3h、6h、12h及24h不同的時間點(diǎn)，，采用全自動生化儀檢測血清胰淀粉酶（AMY）、乳酸脫氫酶（LDH）及肌酸激酶同工酶（CK-MB）的變化，HE染色觀察大鼠胰腺及心臟組織的形態(tài)學(xué)變化，Western blot法及免疫熒光法檢測大鼠心肌組織P-GSK-3β的表達(dá)情況，線粒體腫脹實(shí)驗測定大鼠心肌線粒體吸光度的變化，離體大鼠心臟灌流實(shí)驗觀察牛磺膽酸鈉對大鼠心肌組織P-GSK-3β的表達(dá)影響。 結(jié)果1.血清酶檢測結(jié)果顯示，與0h組相比，各模型組的胰淀粉酶、乳酸脫氫酶及肌酸激酶同工酶都有所升高，其中以12h升高的最為顯著（P 0.05）。2.HE染色結(jié)果顯示，胰腺：與0h組相比，各模型組胰腺組織都不同程度的損害，3h:間質(zhì)血管擴(kuò)張出血，伴有大量炎性細(xì)胞浸潤，實(shí)質(zhì)變化不明顯。6h：大面積的胰腺小葉出血壞死，間質(zhì)血管擴(kuò)張出血，并伴有胰管、膽管的出血壞死；12h：出現(xiàn)了邊緣小葉及胰管的出血壞死，伴有大量的纖維素滲出；24h：除有胰腺出血壞死的表現(xiàn)外，部分區(qū)域的胰腺小葉纖維組織增生明顯，小胰管增生顯著。心臟：與0h組相比，各模型組心臟組織都出現(xiàn)了不同程度的損害。3h：肌間隙增寬，間質(zhì)有輕度的血管擴(kuò)張出血；6h：心肌組織肌間隙增大增寬，間質(zhì)有少量的毛細(xì)血管擴(kuò)張充血；12h：除肌間隙增寬外，出現(xiàn)了嚴(yán)重的肌肉的排列紊亂現(xiàn)象，部分區(qū)域甚至出現(xiàn)了心肌細(xì)胞的變性、腫脹，心肌間質(zhì)血管擴(kuò)張充血，比3h、6h加重；24h：心肌間隙增寬，出現(xiàn)點(diǎn)狀、灶狀及片狀的炎性細(xì)胞浸潤，以中性分葉核白細(xì)胞及中性單核細(xì)胞為主，部分區(qū)域的肌間隙里面還有彌漫性分布的炎性細(xì)胞，類似心肌炎的表現(xiàn)。3.Western blot及免疫熒光結(jié)果顯示，與0h組相比，各模型組心肌組織P-GSK-3β的表達(dá)都有所增加，且以12h升高的最為明顯（P 0.05）。4.線粒體腫脹實(shí)驗結(jié)果顯示，各組心肌線粒體吸光度都有不同程度的減少，且以12h減少最多（P 0.05），5.離體大鼠心臟灌流實(shí)驗結(jié)果顯示，�；悄懰徕c灌流離體大鼠心臟后，心肌組織中P-GSK-3β的表達(dá)情況與對照組相比，無明顯變化。 結(jié)論1）大鼠急危重癥胰腺炎在12h并發(fā)的心肌損害最為嚴(yán)重。 2）P-GSK-3參與到急危重癥胰腺炎并發(fā)的心肌損害作用中。 3）在大鼠急危重癥胰腺炎并發(fā)的心肌損害中，P-GSK-3水平增加并不抑制mPTP的開放。
[Abstract]:Objective the death rate of severe acute pancreatitis (SAP) complicated with cardiac damage is very high, which is a serious threat to the life of the patients.The mechanism of its occurrence was discussed by molecular biological methods, and the theoretical basis was provided for the development of rational clinical drug use.The changes of serum amylase, lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MBB) were detected by automatic biochemical instrument. The morphological changes of rat pancreas and heart tissue were observed by HE staining. Western blot method and immunofluorescence assay were used to detect myocardial changes in rats.The expression of P-GSK-3 尾 in tissues,Mitochondrial swelling test was used to measure the changes of myocardial mitochondrial absorbance in rats, and the effects of sodium taurocholate on the expression of P-GSK-3 尾 in isolated rat hearts were observed.Result 1.The results of serum enzyme detection showed that the levels of amylase, lactate dehydrogenase and creatine kinase isozymes in each model group were higher than those in 0h group. The results of P 0.05).2.HE staining at 12 h showed that the pancreas: compared with the 0 h group, the serum amylase, lactate dehydrogenase and creatine kinase isozymes in each model group were higher than those in the 0 h group.In each model group, pancreatic tissue was damaged for 3 h in varying degrees: interstitial vasodilation, massive inflammatory cell infiltration, no significant changes in parenchyma, large area of pancreatic lobular hemorrhage, interstitial vascular dilatation and hemorrhage, and pancreatic duct.Heart: compared with 0 h group, each model group showed different degrees of damage. 3 h: muscle space widened, interstitial vasodilation hemorrhage 6 h, myocardial tissue muscle space enlarged and widened.There was a small amount of capillary dilatation in the interstitial for 12 h: in addition to the widening of the muscle space, there was a serious disorder of muscle arrangement, and some areas even showed degeneration, swelling, hyperemia of the myocardial interstitial vessels.Compared with 3 h or 6 h, the myocardial space was widened, and the infiltration of focal and flake inflammatory cells was observed. The majority of them were neutrophilic lobular leukocytes and neutrophil mononuclear cells, and there were diffuse inflammatory cells in some areas of muscle space.The results of mitochondria swelling test showed that the absorbance of myocardial mitochondria in each group was decreased in varying degrees, and the maximum decrease was at 12 hours (P 0.05).The results of isolated rat heart perfusion experiment showed that the expression of P-GSK-3 尾 in myocardium of isolated rat heart after perfusing with sodium taurocholate had no significant change compared with that of control group.Conclusion 1) the myocardial damage of acute severe pancreatitis in rats was the most serious at 12 hours.2)P-GSK-3 is involved in myocardial damage caused by acute and severe pancreatitis.3) the increased level of P-GSK-3 did not inhibit the opening of mPTP.
【學(xué)位授予單位】：河北聯(lián)合大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R576

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