【摘要】：急性胰腺炎(Acute pacreatitis,AP)是一種常見的臨床急性腹部疾病,近年來發(fā)病率持續(xù)升高,但市場(chǎng)上尚未有治療AP的特效藥。與AP相關(guān)的腸道損傷將反過來加重的病情惡化。此研究旨在探究一種提取自檸檬的低酯果膠(Low-methoxyl pectin,LMP)是否可以減輕AP嚴(yán)重程度及其相關(guān)腸黏膜屏障損傷。本研究將BALB/c小鼠隨機(jī)分成正常對(duì)照組、急性胰腺炎模型組、低酯果膠組,通過雨蛙素(Caerulein,CAE)過度刺激誘導(dǎo)AP模型,收取血清、胰腺、結(jié)腸、回腸等樣品。通過測(cè)定小鼠血清淀粉酶水平、血清脂肪酶水平、胰腺髓過氧化物酶活力、胰腺水腫程度研究低酯果膠是否能夠減輕急性胰腺炎嚴(yán)重程度;通過測(cè)定血清及胰腺中TNF-α、IL-1β及IL-6的水平研究低酯果膠是否可以降低AP病程中炎癥因子的分泌;通過測(cè)定血清內(nèi)毒素含量,腸道中緊密連接蛋白ZO-1及Occuldin和抗菌肽DEFB1及CRAMP的表達(dá)水平,小鼠糞便中短鏈脂肪酸水平研究低酯果膠是否可以保障AP小鼠腸道屏障功能;通過測(cè)定腸道中TNF-α、IL-1β及IL-6的水平研究低酯果膠是否可以減輕AP小鼠腸道炎癥反應(yīng)。實(shí)驗(yàn)結(jié)果發(fā)現(xiàn)膳食補(bǔ)充低酯果膠后,小鼠的AP嚴(yán)重程度降低,表現(xiàn)為血清淀粉酶及脂肪酶水平,胰腺水腫程度及髓過氧化物酶活性的降低。胰腺組織病理切片的組織學(xué)檢查也證實(shí)了低酯果膠的保護(hù)作用。膳食補(bǔ)充低酯果膠還可以抑制胰腺中促炎細(xì)胞因子的分泌,包括TNF-α,IL-1β和IL-6。此外,膳食補(bǔ)充低酯果膠恢復(fù)了AP相關(guān)腸道屏障的損傷,如上調(diào)了腸道緊密連接蛋白Occludin及ZO-1和抗菌肽DEFB1及Cramp的表達(dá),增加了小鼠腸道短鏈脂肪酸的產(chǎn)量。并且,與CAE組相比,膳食補(bǔ)充了低酯果膠的AP小鼠表現(xiàn)出腸道炎癥反應(yīng)被抑制,結(jié)腸及回腸的促炎細(xì)胞因子分泌減少。綜上,低酯果膠可以通過保障腸道屏障功能從而減輕小鼠AP的嚴(yán)重程度。本研究的實(shí)驗(yàn)結(jié)果表明,低酯果膠可作為有效的營養(yǎng)干預(yù)手段減輕AP的嚴(yán)重程度及相關(guān)腸道屏障損傷。該保護(hù)作用的機(jī)制可能跟低酯果膠的炎癥抑制與腸道黏膜屏障功能的保護(hù)作用有關(guān)。低酯果膠作為一種安全健康的可溶性膳食纖維,或許可將其開發(fā)成AP相關(guān)功能性食品,以更好地預(yù)防、緩解AP。
[Abstract]:Acute pancreatitis (AP) is a common clinical acute abdominal disease, the incidence of which has been increasing in recent years, but there is no specific drug to treat AP in the market. Intestinal injury associated with AP will in turn worsen the condition. The aim of this study was to investigate whether a Low-methoxyl pectin extracted from lemon can reduce the severity of AP and its associated intestinal mucosal barrier damage. In this study, BALB/c mice were randomly divided into normal control group, acute pancreatitis model group and low-ester pectin group. AP model was induced by excessive stimulation of Caerulein (CAE). Serum, pancreas, colon and ileum were collected. The levels of serum amylase, serum lipase, the activity of pancreatic myeloperoxidase and the degree of pancreatic edema were measured to study whether low ester pectin could reduce the severity of acute pancreatitis. To study whether low ester pectin can reduce the secretion of inflammatory factors in the course of AP, to determine the levels of TNF- 偽 -IL-1 尾 and IL-6 in serum and pancreas, and to determine the expression of ZO-1, Occuldin, DEFB1 and CRAMP in intestinal tract by measuring the content of endotoxin in serum. Effects of low Ester Pectin on intestinal Barrier function in AP mice and the effects of low Ester Pectin on intestinal inflammation in AP mice were studied by measuring the levels of TNF- 偽 -TNF- 偽 -IL-1 尾 and IL-6. The results showed that the severity of AP in mice decreased after dietary supplementation of low ester pectin, including the decrease of serum amylase and lipase levels, pancreatic edema and myeloperoxidase activity. Histological examination of pancreatic histopathological sections also confirmed the protective effect of low-ester pectin. Dietary supplementation of low ester pectin also inhibited the secretion of pro-inflammatory cytokines, including TNF- 偽, IL-1 尾 and IL-6. In addition, dietary supplementation of low-ester pectin restored the injury of the intestinal barrier associated with AP, such as up-regulating the expression of Occludin and ZO-1, DEFB1 and Cramp, and increasing the production of short-chain fatty acids in the intestinal tract of mice. In addition, compared with CAE group, AP mice fed with low-ester pectin diet showed inhibition of intestinal inflammatory response and decreased secretion of inflammatory cytokines in colon and ileum. In conclusion, low-ester pectin can reduce the severity of AP by protecting intestinal barrier function in mice. The results showed that low ester pectin could be used as an effective nutritional intervention to alleviate the severity of AP and related intestinal barrier damage. The protective mechanism may be related to the inflammatory inhibition of low-ester pectin and the protective effect of intestinal mucosal barrier function. As a safe and healthy soluble dietary fiber, low ester pectin may be developed into AP related functional food for better prevention and relief of APs.
【學(xué)位授予單位】：江南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R576;TS201.4

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