本文選題：Exendin-4 + 燒傷�。� 參考：《中國(guó)人民解放軍醫(yī)學(xué)院》2015年碩士論文

【摘要】：目的：燒傷后容易發(fā)生以“高糖血癥”為表現(xiàn)的糖代謝障礙,容易引起不良預(yù)后。研究表明,燒傷后糖代謝障礙與胰腺損傷密切相關(guān)。Exendin-4是一種GLP-1受體激動(dòng)劑,并具有高糖依賴(lài)的胰島素促泌作用,且不會(huì)導(dǎo)致低血糖。近年來(lái)研究報(bào)道Exendin-4能抑制氧化應(yīng)激、炎癥和凋亡,而目前Exendin-4保護(hù)嚴(yán)重?zé)齻笠认贀p傷的機(jī)制尚缺乏研究。因此,本研究擬探討Exendin-4對(duì)嚴(yán)重燙傷大鼠早期胰腺損傷的影響與機(jī)制。方法：成年健康Wistar大鼠96只,隨機(jī)分為假燙組、假燙給藥組、燙傷組和燙傷給藥組,每組24只。燙傷組和燙傷給藥組大鼠背部浸于94。C熱水12秒,腹部6秒,制備50%TBSAⅢ°燙傷模型,假燙組和假燙給藥組使用37℃溫水,其余處理相同。燙傷給藥組和假燙給藥組傷后立即于皮下注射Exendin-4 (4ug/kg),并于傷后每天8：00和20：00分別給藥一次,其它組大鼠同時(shí)以相同方式給予相同劑量的滅菌注射用水。傷后1d、3d和5d,剪尾法采血檢測(cè)各組大鼠空腹血糖濃度；放射免疫法檢測(cè)血清胰島素濃度；干濕質(zhì)量法計(jì)算胰腺組織含水量；HE染色觀察胰腺形態(tài)變化；硫代巴比妥酸法檢測(cè)胰腺組織丙二醛(MDA)含量；免疫組織化學(xué)法分析胰腺誘導(dǎo)性一氧化氮合酶(iNOS)表達(dá)水平；免疫印跡法分析胰腺組織3-硝基硝基絡(luò)氨酸(3-NT)、B細(xì)胞淋巴瘤-2相關(guān)X蛋白(Bax)蛋白、活化部分半胱氨酸天冬氨酸蛋白酶3(Cleaved caspase-3)表達(dá)水平。結(jié)果：假燙組和假燙給藥組大鼠傷后各時(shí)相點(diǎn)空腹血糖濃度均無(wú)明顯升高或降低；燙傷組大鼠傷后1d、3d和5d空腹血糖濃度顯著高于假燙組和假燙給藥組；燙傷給藥組大鼠傷后1d和3d空腹血糖濃度顯著低于燙傷組；燙傷給藥組大鼠傷后1d空腹血糖濃度顯著高于假燙組和假燙給藥組。假燙組和假燙給藥組大鼠各時(shí)相點(diǎn)空腹血清胰島素濃度均無(wú)明顯升高或降低；燙傷組大鼠傷后各時(shí)相點(diǎn)空腹血清胰島素濃度均顯著高于假燙組和假燙給藥組；燙傷給藥組大鼠傷后各時(shí)相點(diǎn)空腹血清胰島素濃度均顯著高于燙傷組。假燙組和假燙給藥組大鼠傷后各時(shí)相點(diǎn)胰腺組織含水量均無(wú)明顯升高或降低；燙傷組和燙傷給藥組大鼠傷后1d胰腺組織含水量顯著高于假燙組和假燙給藥組；與燙傷組比較,燙傷給藥組大鼠胰腺組織含水量無(wú)明顯升高或降低。HE染色結(jié)果顯示,假燙組和假燙給藥組大鼠傷后各時(shí)相點(diǎn)胰島形態(tài)規(guī)則,β細(xì)胞數(shù)量豐富,分布均勻,排列緊密,胞漿濃染,偶見(jiàn)空泡樣改變；燙傷組大鼠傷后1d即出現(xiàn)胰島空泡樣變和p細(xì)胞數(shù)量減少,傷后3d胰島內(nèi)出現(xiàn)廣泛空泡樣變,p細(xì)胞數(shù)量顯著減少,傷后5d胰島空泡樣變輕于傷后3d,β細(xì)胞數(shù)量多于傷后3d；燙傷給藥組大鼠傷后各時(shí)相點(diǎn)胰島空泡樣變均輕于燙傷組,β細(xì)胞數(shù)量均多于燙傷組。假燙組和假燙給藥組大鼠傷后各時(shí)相點(diǎn)胰腺組織丙二醛(MDA)含量均無(wú)明顯升高或降低；燙傷組大鼠傷后各時(shí)相點(diǎn)胰腺組織丙二醛(MDA)含量均顯著高于假燙組和假燙給藥組；燙傷給藥組大鼠傷后1d和3d胰腺組織丙二醛(MDA)含量均顯著高于假燙組和假燙給藥組；與燙傷組比較,燙傷給藥組大鼠傷后5d胰腺組織丙二醛(MDA)含量低于燙傷組。免疫組化結(jié)果顯示,假燙組和假燙給藥組大鼠傷后各時(shí)相點(diǎn)胰島誘導(dǎo)型一氧化氮合酶(iNOS)表達(dá)水平均無(wú)明顯升高或降低；燙傷組大鼠傷后各時(shí)相點(diǎn)胰島誘導(dǎo)型一氧化氮合酶(iNOS)表達(dá)水平均高于假燙組和假燙給藥組；燙傷給藥組大鼠傷后各時(shí)相點(diǎn)胰島誘導(dǎo)型一氧化氮合酶(iNOS)表達(dá)水平均低于燙傷組,高于假燙組和假燙給藥組。Western Blot結(jié)果顯示,假燙組和假燙給藥組大鼠傷后各時(shí)相點(diǎn)胰腺組織3-硝基酪氨酸(3-NT)蛋白水平表達(dá)水平均無(wú)明顯升高或降低；傷后3d和5d,燙傷組大鼠胰腺組織3-NT蛋白表達(dá)水平顯著高于假燙組和假燙給藥組；傷后3d和5d,燙傷給藥組大鼠胰腺組織3-NT蛋白表達(dá)水平顯著低于燙傷組,顯著高于假燙組和假燙給藥組。Western Blot結(jié)果顯示,假燙組和假燙給藥組大鼠傷后各時(shí)相點(diǎn)胰腺組織Bcl-2相關(guān)X(Bax)蛋白表達(dá)水平均無(wú)明顯升高或降低；傷后3d和5d,燙傷組大鼠胰腺組織Bax蛋白表達(dá)水平顯著高于假燙組和假燙給藥組；傷后3d和5d,燙傷給藥組大鼠胰腺組織Bax蛋白表達(dá)水平低于燙傷組,顯著高于假燙組和假燙給藥組。Western Blot結(jié)果顯示,假燙組和假燙給藥組大鼠傷后各時(shí)相點(diǎn)胰腺組織Cleaved caspase-3蛋白表達(dá)水平比值均無(wú)明顯升高或降低；燙傷組大鼠傷后各時(shí)相點(diǎn)胰腺組織Cleaved caspase-3蛋白表達(dá)水平顯著高于假燙組和假燙給藥組；燙傷給藥組大鼠傷后各時(shí)相點(diǎn)胰腺組織Cleaved caspase-3蛋白表達(dá)水平低于燙傷組,高于假燙組和假燙給藥組。結(jié)論：皮下注射Exendin-4可抑制胰腺脂質(zhì)和蛋白質(zhì)過(guò)氧化損傷,抑制胰腺過(guò)度炎癥和凋亡級(jí)聯(lián)反應(yīng),改善胰腺損傷程度,增加胰島p細(xì)胞數(shù)量,促進(jìn)嚴(yán)重燙傷大鼠傷后胰島素分泌,降低空腹血糖濃度,但不會(huì)導(dǎo)致低血糖。
[Abstract]:Objective: it is easy to produce glucose metabolism disorder characterized by hyperglycemia after burn. The study shows that.Exendin-4 is a kind of GLP-1 receptor agonist, which is closely related to pancreatic injury after burn, and has high glucose dependent insulin secretion and does not lead to hypoglycemia. Exendin-4 can inhibit oxidative stress, inflammation and apoptosis, but the mechanism of Exendin-4 protection of pancreatic injury after severe burns is still lacking. Therefore, this study intends to explore the effect and mechanism of Exendin-4 on early pancreatic injury in severely scalded rats. Methods: 96 adult healthy Wistar rats were randomly divided into a sham perm group, an ironing group, and a perm group. The injured group and scald group were treated with 24 rats in each group. The rats in the scald group and the scald group were immersed in 94.C hot water for 12 seconds and the abdomen was 6 seconds, and the 50%TBSA III degree scald model was prepared. The rest treatment group and the fake ironing group were treated with warm water at 37 C, the rest treatment was the same. Exendin-4 (4ug/kg) was injected subcutaneously after the injury to the scald group and the sham perm group. After injury, each group was injured after injury. The same dosage of Sterile Water for Injection was given at 8:00 and 20:00 respectively. The rats in the other groups were given the same dose of Sterile Water for Injection in the same way. After injury, 1D, 3D and 5D were used to detect the concentration of fasting blood glucose in each group; the concentration of serum insulin was detected by radioimmunoassay; the moisture content of the pancreas was calculated by the dry wet mass method; HE staining was used to observe the pancreas shape. The content of malondialdehyde (MDA) in pancreatic tissue was detected by thiobarbituric acid; the expression of pancreatic inducible nitric oxide synthase (iNOS) was analyzed by immunohistochemistry; 3- nitro nitroso (3-NT), B cell lymphoma, -2 phase X protein (Bax) protein and activated partial cysteine aspartic acid were activated by immunoblotting The expression level of protease 3 (Cleaved caspase-3). Results: there was no significant increase or decrease in the concentration of fasting blood glucose at each time point in the rats of sham and sham ironing group. The concentration of fasting blood glucose in 1D, 3D and 5D after injury in the scald group was significantly higher than that in the sham group and the false ironing group; the concentration of 1D and 3D after injury in the scald group was significantly higher than that of the rats. The concentration of 1D's fasting blood glucose in the scald group was significantly higher than that of the sham group and the fake ironing group. The serum insulin concentration in the fasting serum at each time point in the sham group and the fake ironing group was not significantly elevated or decreased, and the concentration of the serum isshap in the fasting serum at each time point in the scald group was significantly higher than that of the sham group and the false scald group. In the scald group, the concentration of serum insulin in the fasting serum was significantly higher than that of the scald group. The water content of the pancreatic tissue in the rats of the sham group and the fake ironing group was not significantly increased or decreased, and the water content of the 1D pancreatic tissue in the scald group and the scald group was significantly higher than that of the sham group and the false scald group. Compared with the scald group, the water content in the pancreas tissue of the rats in the scald group was not significantly increased or decreased by the.HE staining results. The islet morphologic rules of the rats after the injury were found in the sham group and the false ironing group. The number of the beta cells was rich, the distribution was uniform, the cytoplasm was dense, and the vacuolated changes were found, and the rats in the scald group were 1D after injury. The number of the islet vacuoles and the number of P cells decreased, and the number of P cells decreased significantly in the 3D islets after injury. The number of 5D islet vacuoles was lighter than 3D after injury, and the number of beta cells was more than that of 3D after injury. The islet vacuoles in the scald group were all lighter than those in the scald group after injury. The content of malondialdehyde (MDA) in the pancreatic tissue of the rats of the sham group and the fake ironing group did not increase or decrease, and the content of the malondialdehyde (MDA) in the pancreatic tissue of the scald group was significantly higher than that of the false ironing group and the false ironing group. The content of the malondialdehyde (MDA) in the pancreas tissue of the rats in the scald group after injury was significantly higher than that of the rats in the scald group. Compared with the scald group and the scald group, the content of 5D pancreatic tissue malondialdehyde (MDA) in the scald group was lower than that of the scald group. The immunohistochemical results showed that the expression level of the islet induced nitric oxide synthase (iNOS) in the rats of the sham and sham group was not significantly increased or decreased after the injury. The expression level of islet inducible nitric oxide synthase (iNOS) in each phase point of rats after injury was higher than that in the sham group and the false ironing group, and the expression level of islet induced nitric oxide synthase (iNOS) in the rats after injury was lower than that in the scald group. The results of.Western Blot in the sham group and the sham ironing group showed that the sham group and the false ironing group were false and false. The level of the expression level of 3- nitrotyrosine (3-NT) protein in the pancreatic tissue of the rats after injury was not significantly increased or decreased, and the expression level of 3-NT protein in the pancreas tissue of the rats after injury was significantly higher than that of the sham group and the false ironing group in 3D and 5D after injury. The level of 3-NT protein expression in the pancreas tissue of the rats after injury was 3D and 5D. Significantly lower than the scald group, significantly higher than the false ironing group and the false ironing group.Western Blot results showed that the Bcl-2 related X (Bax) protein expression level in the pancreatic tissue of the rats of the sham group and the false ironing group did not increase or decrease, and the expression level of Bax protein in the pancreas tissue of the rats after injury 3D and 5D, and in the scald group was significantly higher than that of the sham group The expression level of Bax protein in pancreas tissue of rats with 3D and 5D after injury was lower than that of scald group, which was significantly higher than that of false ironing group and false ironing group.Western Blot. The ratio of Cleaved caspase-3 protein expression level in each phase point of the rats of sham perm group and false ironing group had no significant increase or decrease. In the scald group, the expression level of Cleaved caspase-3 protein in the pancreatic tissue of the rats after injury was significantly higher than that of the sham group and the false ironing group. The expression level of Cleaved caspase-3 protein in the pancreatic tissue of the scalded rats after injury was lower than that in the scald group, which was higher than that of the sham group and the false ironing group. Conclusion: the subcutaneous injection of Exendin-4 can be used as a result. Inhibition of pancreatic lipid and protein peroxidation damage, inhibition of pancreatic excessive inflammation and apoptosis cascade reaction, improve the degree of pancreatic injury, increase the number of islet P cells, promote insulin secretion in severely scalded rats, reduce the concentration of fasting blood glucose, but do not lead to hypoglycemia.

【學(xué)位授予單位】：中國(guó)人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R644

【共引文獻(xiàn)】

相關(guān)期刊論文 前1條

1 張秀麗;魯淑敏;趙越;胡曄;馬健飛;李德天;;鋅離子對(duì)脂多糖作用下大鼠腹膜間皮細(xì)胞凋亡的影響[J];中國(guó)中西醫(yī)結(jié)合腎病雜志;2013年12期

相關(guān)博士學(xué)位論文 前4條

1 胡世偉;巖藻糖基化海參硫酸軟骨素改善胰島素抵抗及其作用機(jī)制的研究[D];中國(guó)海洋大學(xué);2014年

2 錢(qián)晶;游離脂肪酸受體GPR40對(duì)胰腺β細(xì)胞胰島素合成分泌的調(diào)控及配體不依賴(lài)受體內(nèi)吞機(jī)制的研究[D];浙江大學(xué);2014年

3 范能光;前脂肪因子介導(dǎo)的胰島素抵抗慢性炎癥機(jī)制以及GLP-1的抗炎作用研究[D];上海交通大學(xué);2014年

4 郭健;基于硅藻傳遞的珍珠貝硒蛋白提取及對(duì)心肌細(xì)胞抗氧化活性研究[D];東華大學(xué);2015年

相關(guān)碩士學(xué)位論文 前3條

1 崔岱;胰高糖素樣肽1對(duì)大鼠胰島功能調(diào)控的研究[D];南京醫(yī)科大學(xué);2005年

2 黃瓊珠;GLP-1類(lèi)似物對(duì)2型糖尿病大鼠腎臟的保護(hù)作用及其可能機(jī)制[D];福建醫(yī)科大學(xué);2014年

3 劉真真;艾塞那肽對(duì)棕櫚酸作用下大鼠胰島β細(xì)胞FTO表達(dá)及氧化應(yīng)激的影響[D];鄭州大學(xué);2014年

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