發(fā)布時(shí)間：2018-03-06 09:05

  本文選題：重癥急性胰腺炎　切入點(diǎn)：高脂血癥性胰腺炎　出處：《瀘州醫(yī)學(xué)院》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：高脂血癥性胰腺炎臨床上一般又稱作高甘油三酯血癥性胰腺炎，隨著人們生活水平的提高和飲食結(jié)構(gòu)的改變，其發(fā)病率逐漸上升，目前是僅次于膽源性胰腺炎和酒精性胰腺炎的第三大病因，，約占1.3%—3.8%。但高脂血癥性胰腺炎的發(fā)病機(jī)制目前尚無(wú)法得到統(tǒng)一的認(rèn)定，主要集中在游離脂肪酸的毒性作用，鈣超載的誘導(dǎo)作用以及基因突變方面的研究。結(jié)合新近的論點(diǎn)，本課題針對(duì)鈣超載誘導(dǎo)機(jī)制，做更進(jìn)一步的研究。 目的：應(yīng)用鈣通道阻滯劑維拉帕米作用于高脂血癥性胰腺炎大鼠，通過(guò)觀察其療效，探討鈣超載在高脂血癥性胰腺炎發(fā)病機(jī)制中的作用及意義，從而為維拉帕米作為高脂血癥性胰腺炎治療新藥物提供理論依據(jù)。方法：80只SD雄性大鼠，體重為200-250g，隨機(jī)分為四組，每組20只，假手術(shù)組（SO組）：普通乳劑飼料（普通飼料+適量蒸餾水），對(duì)大鼠進(jìn)行灌胃，持續(xù)兩周，兩周后開(kāi)腹并用空針穿刺胰膽管，不注射任何物質(zhì)，然后退針關(guān)腹。重癥胰腺炎組（SAP組）：普通乳劑飼料灌胃兩周的大鼠，開(kāi)腹后胰膽管逆行緩慢推注5%�；悄懰徕c，后關(guān)腹。高脂血癥性胰腺炎組（HLP組）：高脂灌胃劑（20%豬油+10%膽固醇+20%吐溫80+2%膽酸鈉+1%丙基硫氧嘧啶+適量蒸餾水）灌胃兩周后，胰膽管穿刺推注5%�；悄懰徕c，關(guān)腹。維拉帕米治療組（CCB組）：高脂血癥性胰腺炎造模后10分鐘，給予腹腔注射維拉帕米1mg/kg。術(shù)前經(jīng)頸靜脈或心臟采血檢測(cè)其甘油三酯（triglyceride，TG）水平；手術(shù)24小時(shí)后，統(tǒng)計(jì)死亡例數(shù)，處死所有大鼠，觀察并記錄腹水量；用酶聯(lián)免疫吸附法（ELISA法）測(cè)定血清血栓素A2（TXA2）及血小板活化因子（PAF）的含量；取適量胰腺組織，用蘇木精-伊紅染色（HE染色），顯微鏡下觀察其胰腺病理改變，并對(duì)胰腺組織損傷進(jìn)行病理學(xué)評(píng)分；取適量胰腺組織用流式細(xì)胞儀技術(shù)檢測(cè)細(xì)胞內(nèi)鈣離子水平；用Western印跡法分析NF-κBp65蛋白的表達(dá)。結(jié)果：1.SO組大鼠無(wú)一死亡，HLP組死亡7只，SAP組死亡4只，CCB組死亡2只。2.SAP組、HLP組、CCB組均有大量血性腹水，而SO組幾乎沒(méi)有腹水；HLP組、CCB組TG水平均較SO組和SAP組顯著升高，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。3.胰腺組織損傷病理評(píng)分： HLP組、SAP組炎癥，水腫，出血，壞死均較SO組顯著增高（P0.05）,HLP組損傷水平較SAP組高（P0.05），而CCB組炎癥水腫出血壞死水平又明顯比HLP組低（P0.05）。4. HLP組與SAP組TXA2、PAF含量均較對(duì)照組顯著升高（P0.05），HLP組又高于SAP組（P0.05），而CCB組TXA2、PAF含量均低于HLP組，差異有統(tǒng)計(jì)學(xué)意義（P0.05）。5.鈣離子水平： HLP組與SAP組顯著高于SO組（P0.05），HLP組鈣離子也高于SAP組，差異有統(tǒng)計(jì)學(xué)意義（P0.05），而CCB組與HLP組比較又顯著性降低（P0.05）。6. NF-κBp65蛋白表達(dá)： HLP組與SAP組NF-κBp65蛋白表達(dá)強(qiáng)度及陽(yáng)性率均較對(duì)照組顯著升高（P0.05），而HLP組NF-κBp65蛋白表達(dá)強(qiáng)度及陽(yáng)性率與SAP組、CCB組又有顯著性差異（P0.05）。結(jié)論：1．用改進(jìn)型的高脂乳劑（20%豬油+10%膽固醇+20%吐溫80+2%膽酸鈉+1%丙機(jī)硫氧嘧啶+適量蒸餾水）進(jìn)行灌胃，持續(xù)兩周，可成功建立高脂血癥大鼠模型；胰膽管逆行推注5%牛磺膽酸鈉也可成功建立重癥急性胰腺炎。2．高脂血癥性胰腺炎較普通型胰腺炎大鼠的病情更重，說(shuō)明高血脂在胰腺炎的發(fā)生、發(fā)展上起到了重要的推動(dòng)作用。3．通過(guò)運(yùn)用鈣通道阻滯劑維拉帕米抑制胰腺腺泡細(xì)胞內(nèi)鈣超載，可適當(dāng)減輕高脂血癥性胰腺炎大鼠的病情程度，說(shuō)明鈣超載參與了高脂血癥性胰腺炎的病變過(guò)程，也說(shuō)明應(yīng)用維拉帕米治療高脂血癥性胰腺炎有效。
[Abstract]:Hyperlipidemic pancreatitis clinical commonly called hypertriglyceridemia pancreatitis, with the improvement of people's living standard and the change of diet structure, the incidence increased gradually, is currently the third leading cause after biliary pancreatitis and alcoholic pancreatitis, accounting for about 1.3% of 3.8%. but the pathogenesis of hyperlipidemic pancreatitis there is no unified identification, mainly focused on the toxic effects of free fatty acids, research and the role of gene mutation induced by calcium overload. Combined with the recent arguments, the topic for the calcium overload induced mechanism, do further research.
Objective: the application of calcium channel blockers Vera Pammy effect on hyperlipidemic pancreatitis rats by observing its efficacy, to investigate the significance and calcium overload in hyperlipidemic pancreatitis pathogenesis, so as to provide a theoretical basis for new drugs for Vera Pammy as hyperlipidemic pancreatitis. Methods: 80 male SD rats. The weight of 200-250g, were randomly divided into four groups, 20 rats in each group, sham operation group (group SO): ordinary emulsion feed (normal diet and proper amount of distilled water), the rats were given orally for two weeks, two weeks after the open and empty needle puncture of pancreatic duct, with no substance, then the needle closed abdomen. Severe acute pancreatitis group (SAP group): ordinary feed emulsion by gavage for two weeks in rats after laparotomy and retrograde cholangiopancreatography slow infusion of 5% sodium taurocholate, after abdominal closure. Hyperlipidemic pancreatitis group (HLP group): high fat stomach perfusion agent (20% lard +10% cholesterol +20% Twain 80+2% +1% sodium cholate propylthiouracil + water) after two weeks, the pancreatic duct puncture injection of 5% sodium taurocholate, the abdomen was closed. Vera Pammy treatment group (CCB group): 10 minutes of hyperlipidemic pancreatitis model after intraperitoneal injection of Vera Pammy 1mg/kg. before operation through the jugular vein or heart blood test the triglyceride level (triglyceride, TG); 24 hours after the surgery, the statistical number of deaths, all rats were sacrificed, observe and record the amount of ascites; by enzyme-linked immunosorbent assay (ELISA) determination of serum thromboxane A2 (TXA2) and platelet activating factor (PAF) content; proper amount of pancreatic tissue by hematoxylin eosin staining (HE staining), the pathological change of pancreas were observed under microscope, and the pathological score of pancreatic tissue injury; proper amount of pancreatic tissue calcium level by flow cytometry technique in cells was detected by Western blotting analysis of NF; -魏Bp65铔嬬櫧鐨勮〃杈

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