CHL1在炎癥性腸病中的作用及其機(jī)制
發(fā)布時(shí)間：2019-07-02 09:30
【摘要】：炎癥性腸病(Inflammatory bowel disease,IBD)包括潰瘍性結(jié)腸炎(ulcerative colitis)和克羅恩病(Crohn’s disease),這是一種胃腸道的炎癥性疾病,伴隨著嚴(yán)重的病理學(xué)變化,預(yù)后不佳且病因未明。潰瘍性結(jié)腸炎的炎癥主要發(fā)生在粘膜當(dāng)中。最主要的癥狀包括腹瀉,結(jié)腸直腸出血,粘液增多和腹痛�？肆_恩病是一種慢性炎癥,從口到肛門的消化道都可能發(fā)生,主要發(fā)生在回腸,盲腸和結(jié)腸。在克羅恩病的發(fā)生中,炎癥從腸道的粘膜層穿透到漿膜層,具有節(jié)段性不對稱的特征,在某些病人身上可能發(fā)現(xiàn)上皮樣肉芽腫。IBD在歐美國家高發(fā),但根據(jù)最新的研究,在亞洲和南美洲,IBD的患病率也日益增高。IBD的病因主要與環(huán)境、免疫、遺傳等因素有關(guān),但是,慢性炎癥在腸道反復(fù)發(fā)作的機(jī)制尚不清楚。部分觀點(diǎn)認(rèn)為,腸道慢性炎癥的發(fā)生與腸道粘膜免疫缺陷有關(guān)[28]。近年來的研究發(fā)現(xiàn),提示細(xì)胞黏附分子在腸道炎癥發(fā)展的過程中起重要作用。幾種主要的細(xì)胞黏附分子介導(dǎo)了淋巴細(xì)胞的募集,包括選擇素,整合素,鈣黏蛋白和免疫球蛋白超家族。L-選擇素或P-選擇素使得白細(xì)胞被高內(nèi)皮小靜脈捕獲貼壁,通過滾動(dòng),LFA-1與整合素之間形成牢固黏附,α4β1(VLA-4)整合素、α4β7整合素與上皮細(xì)胞上的VCAM-1和MAdCAM-1形成牢固黏附。臨床上諸多藥物是通過抑制細(xì)胞黏附分子(cell adhesion molecule,CAM)對炎癥細(xì)胞的結(jié)合實(shí)現(xiàn)的。比如抑制α4β1 VCAM之間形成牢固黏附的那他珠單抗,抑制α4β7-MAdCAM-1形成牢固黏附的委地落珠單抗。CHL1是一種在人體內(nèi)普遍表達(dá)的神經(jīng)細(xì)胞黏附分子(Neural cell adhesion molecule,NCAM),在以往的研究中,發(fā)現(xiàn)它對成人神經(jīng)回路軸突形成、神經(jīng)元的生長和存活有著至關(guān)重要的作用。另一方面,CHL1與結(jié)直腸癌刪除分子(Deleted in colorectal carcinoma,DCC)有相似的結(jié)構(gòu)域。有研究表明,CHL1在結(jié)腸癌病人的結(jié)腸組織中表達(dá)降低[8,9]。但CHL1與炎癥性腸病之間的關(guān)系尚缺乏探討。炎癥性腸病的發(fā)生往往伴隨著體內(nèi)炎癥因子的增加,以及炎癥細(xì)胞對腸粘膜上皮的浸潤。中性粒細(xì)胞的浸潤在潰瘍性結(jié)腸炎的發(fā)生中,起著關(guān)鍵性的作用,也是衡量疾病活動(dòng)度以及炎癥程度的關(guān)鍵標(biāo)志。正常健康組織中,中性粒細(xì)胞在粘膜固有層少量分布,隨著炎癥進(jìn)行,浸潤到上皮表面或結(jié)腸隱窩,與隱窩的退行性變化和隱窩浸潤有關(guān)。IBD的活動(dòng)度與中性粒細(xì)胞浸潤的發(fā)展、隱窩消失呈正相關(guān)。所以在對于IBD的干擾治療中,中性粒細(xì)胞被認(rèn)為是一種可能的藥理學(xué)靶標(biāo)。在IBD中,由于炎癥反應(yīng)的增強(qiáng),單核細(xì)胞來源的巨噬細(xì)胞往往會(huì)增多,巨噬細(xì)胞對維持胃腸道環(huán)境內(nèi)穩(wěn)態(tài)起至關(guān)重要,同時(shí)可以抵制病原體破壞,以保護(hù)腸道。巨噬細(xì)胞浸潤程度也是一種反應(yīng)炎癥程度的標(biāo)志。本研究利用葡聚糖硫酸鈉(Dextran Sulfate Sodium,DSS)誘導(dǎo)的小鼠結(jié)腸炎模型,探討了CHL1缺失對DSS誘導(dǎo)的小鼠結(jié)腸炎癥的影響,研究中性粒細(xì)胞和巨噬細(xì)胞浸潤對促進(jìn)結(jié)腸炎癥反應(yīng)和組織損傷的機(jī)制。主要的研究結(jié)果如下:1.炎癥性腸病上調(diào)小鼠結(jié)腸組織CHL1的表達(dá)為了探索炎癥性腸病與神經(jīng)黏附分子CHL1的關(guān)系,建立經(jīng)典的DSS小鼠炎癥性腸病模型。在DSS誘導(dǎo)炎癥性腸病的第5天,第7天,第9天,檢測小鼠結(jié)腸組織CHL1組織的表達(dá)。在蛋白水平上,從誘導(dǎo)炎癥性腸病的第5天開始,CHL1的表達(dá)上升,第7天和第9天CHL1的表達(dá)持續(xù)性增高。在轉(zhuǎn)錄水平,實(shí)時(shí)定量PCR(Q-PCR)檢測CHL1 mRNA的表達(dá)。從第7天開始,CHL1在mRNA水平的表達(dá)顯著增加。這說明不論在轉(zhuǎn)錄水平還是蛋白表達(dá)水平,炎癥性腸病小鼠結(jié)腸組織CHL1的表達(dá)都是上調(diào)的。2.CHL1缺失加重炎癥性腸病的發(fā)生為了進(jìn)一步探索CHL1與炎癥性腸病的關(guān)系,將CHL1(+/+)型和CHL1(-/-)型小鼠根據(jù)是否喂養(yǎng)DSS分為四組,建立炎癥性腸病模型。發(fā)現(xiàn)與DSS誘導(dǎo)的CHL1(+/+)型小鼠相比,DSS誘導(dǎo)的CHL1(-/-)型小鼠在炎癥性腸病的發(fā)生中便血明顯,從應(yīng)激的第7天開始,體重明顯減輕,在第9天,DSS誘導(dǎo)的CHL1(-/-)型小鼠死亡率明顯增加。檢測小鼠腸組織,DSS誘導(dǎo)的CHL1(-/-)型小鼠結(jié)腸長度明顯縮短,炎細(xì)胞浸潤和組織損傷嚴(yán)重。以上結(jié)果反映了CHL1缺失加重了炎癥性腸病的發(fā)生。3.CHL1缺失引起小鼠結(jié)腸上皮細(xì)胞結(jié)構(gòu)的改變,增加腸道的通透性觀察小鼠結(jié)腸上皮組織形態(tài)學(xué)的變化,發(fā)現(xiàn)CHL1缺失可以使原本排列緊密的小鼠結(jié)腸柱狀上皮細(xì)胞排列變得較為松散,細(xì)胞體積明顯增大,杯狀細(xì)胞增多。在DSS應(yīng)激后,DSS誘導(dǎo)的CHL1(+/+)型小鼠的上皮細(xì)胞排列仍舊有序,而DSS誘導(dǎo)的CHL1(-/-)型小鼠的柱狀上皮細(xì)胞排列明顯紊亂。CHL1(-/-)型小鼠結(jié)腸上段的改變以上皮細(xì)胞細(xì)胞形態(tài)的改變?yōu)橹�。結(jié)腸下段的改變以上皮細(xì)胞細(xì)胞形態(tài)的紊亂為主。結(jié)腸中段的改變介于上段和下段的改變之間。通過FITC檢測腸道通透性,喂養(yǎng)DSS的CHL1(-/-)型小鼠腸道通透性明顯升高。結(jié)腸末端對FITC的截留都是最強(qiáng)的,DSS誘導(dǎo)的CHL1(-/-)型小鼠對FITC的截留與DSS誘導(dǎo)的CHL1(+/+)型小鼠相比無明顯改變,而DSS誘導(dǎo)的CHL1(-/-)型小鼠結(jié)腸上端、中段對FITC的截留要明顯強(qiáng)于DSS誘導(dǎo)的CHL1(-/-)型小鼠。4.CHL1缺失增加結(jié)腸組織中炎癥細(xì)胞的浸潤為了檢測CHL1缺失影響炎癥性腸病的免疫學(xué)機(jī)制,DSS誘導(dǎo)第5天,第7天檢測外周血中性粒細(xì)胞的表達(dá),發(fā)現(xiàn)與喂養(yǎng)DSS的CHL1(+/+)型小鼠相比,DSS誘導(dǎo)的CHL1(-/-)型小鼠模型外周血中性粒細(xì)胞的數(shù)量并不增高,表明CHL1缺失并不會(huì)促進(jìn)小鼠外周血中中心粒細(xì)胞的增殖分化,但是小鼠結(jié)腸組織中中性粒細(xì)胞的浸潤明顯增多,這種變化很可能是因?yàn)镃HL1的缺失導(dǎo)致。此外,在結(jié)腸組織內(nèi),巨噬細(xì)胞對結(jié)腸組織浸潤也明顯增多。綜上所述,本研究首次觀察到神經(jīng)粘附分子CHL1在腸道組織中表達(dá),并且在炎癥性腸病時(shí)CHL1的表達(dá)明顯升高;CHL1缺失后通過增強(qiáng)炎癥細(xì)胞的浸潤和腸道的通透性,加重炎癥性腸病的發(fā)生。以上結(jié)果提示CHL1在炎癥性腸病的發(fā)生中發(fā)揮重要保護(hù)作用。該研究為炎癥性腸病的干預(yù)提供了新的思路。
[Abstract]:Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is an inflammatory disease in the gastrointestinal tract, with severe pathological changes, poor prognosis and an unknown cause. The inflammation of the ulcerative colitis mainly occurs in the mucous membrane. The most important symptoms include diarrhea, colorectal bleeding, increased mucus, and abdominal pain. Crohn's disease is a chronic inflammation that can occur in the digestive tract from the mouth to the anus, mainly in the ileum, the cecum and the colon. In the occurrence of Crohn's disease, inflammation is penetrated from the mucosal layer of the intestinal tract to the serosa layer, with the characteristics of segmental asymmetry, and epithelial-like granuloma may be found on some patients. IBD is a high incidence in the European and American countries, but the prevalence of IBD is also increasing in Asia and South America, according to the latest study. The etiology of IBD is mainly related to the factors such as environment, immunity, and genetics. However, the mechanism of chronic inflammation in the intestine is not clear. In some view, the occurrence of chronic inflammation of the intestinal tract is related to the intestinal mucosal immune deficiency[28]. In recent years, it has been found that cell adhesion molecules play an important role in the development of intestinal inflammation. Several major cell adhesion molecules mediate the recruitment of lymphocytes, including the selection of the protein, the integrin, the calcium mucin and the immunoglobulin superfamily. L-selectin or P-selectin was used to capture the adherence of the white blood cells to the high-endothelial venules, and a strong adhesion was formed between the LFA-1 and the integrin by rolling, and the VCAM-1 and the MAdCAM-1 on the epithelial cells were firmly adhered to the total of 4-1 (VLA-4) integrin. In clinical, many drugs are achieved by inhibiting the binding of cell adhesion molecules (CAM) to the inflammatory cells. For example, to inhibit the formation of a strong adhesion of the bevacizumab between the babo4 and 1vcam, and to inhibit the formation of a firm-adhered monocytic bevacizumab in the h4-7-mAdCAM-1. CHL1 is a kind of nerve cell adhesion molecule (NCAM) which is widely expressed in human body. In the past study, it has been found that it plays an important role in the formation of axons of adult neural circuits, the growth and survival of neurons. On the other hand, CHL1 and the deletion of colorectal cancer (DCC) have similar domains. Studies have shown that the expression of CHL1 in the colon tissue of patients with colon cancer is reduced[8,9]. However, the relationship between CHL1 and inflammatory bowel disease is still lacking. The occurrence of inflammatory bowel disease is often accompanied by an increase in inflammatory factors in the body, as well as the infiltration of inflammatory cells on the intestinal mucosa epithelium. The infiltration of neutrophils plays a key role in the occurrence of ulcerative colitis, and is a key marker to measure the activity of the disease and the degree of inflammation. In the normal healthy tissue, the neutrophils are distributed in a small amount in the lamina propria, and with the inflammation, infiltration to the epithelial surface or the crypt of the colon is related to the degenerative changes of the crypt and the infiltrates of the crypt. The activity of IBD is related to the development of neutrophil infiltration and the disappearance of the crypt. Neutrophil is considered a potential pharmacological target in the treatment of the interference with IBD. In IBD, monocyte-derived macrophages tend to increase due to the increased inflammatory response, and macrophages are critical to maintaining a steady state in the gastrointestinal environment, while resisting the destruction of pathogens to protect the intestinal tract. The degree of macrophage infiltration is also a sign of the degree of inflammation. In this study, the effect of CHL1 deletion on the colon inflammation induced by DSS was discussed by using Dextran Sulfonate Sodidium (DSS), and the mechanism of the infiltration of neutrophils and macrophages on the inflammatory response and tissue injury of the colon was studied. The main results are as follows:1. In order to explore the relationship between the inflammatory bowel disease and the neuroadhesion molecule CHL1, the expression of CHL1 in the colon tissue of the mouse was up-regulated by inflammatory bowel disease, and the model of the classic DSS mouse inflammatory bowel disease was established. The expression of the CHL1 tissue in the colon tissue of the mouse was detected on Day 5, Day 7, and Day 9 of the DSS-induced inflammatory bowel disease. At the protein level, the expression of CHL1 increased from day 5 of the induction of inflammatory bowel disease, and the expression of CHL1 on Day 7 and Day 9 continued to increase. The expression of CHL1 mRNA was detected by real-time quantitative PCR (Q-PCR) at the level of transcription. From day 7 onwards, the expression of CHL1 at the mRNA level was significantly increased. in ord to further explore that relationship between CHL1 and inflammatory bowel disease, The CHL1 (+/ +) and CHL1 (-/-) mice were divided into four groups according to whether or not the DSS was fed, and an inflammatory bowel disease model was established. In comparison with DSS-induced CHL1 (+/ +)-type mice, DSS-induced CHL1 (-/-)-type mice were significantly reduced in the occurrence of inflammatory bowel disease, with a significant reduction in body weight from day 7 of stress, and a significant increase in the mortality of the CHL1 (-/-)-type mice induced by DSS on Day 9. The length of the colon of the CHL1 (-/-) type mouse induced by DSS was significantly shortened, and the infiltration of the inflammatory cells and the tissue damage were serious. The results indicated that the deletion of CHL1 aggravated the occurrence of inflammatory bowel disease.3. The deletion of CHL1 caused the change of the structure of the colon epithelial cells in the mice, and the changes of the morphology of the epithelial tissue of the colon of the mice were observed by increasing the permeability of the intestinal tract. It was found that the deletion of CHL1 could make the arrangement of the columnar epithelial cells of the colon of the mouse in close alignment to be loose, the volume of the cells increased obviously, and the goblet-like cells increased. After DSS stress, the arrangement of the epithelial cells of the DSS-induced CHL1 (+/ +)-type mice is still in order, while the columnar epithelial cells of the DSS-induced CHL1 (-/-)-type mice are in an obvious disorder. The changes of the upper segment of the colon of the CHL1 (-/-) type mouse were mainly the change of the cell morphology of the epithelial cells. The changes of the lower segment of the colon were dominated by the disorder of the cell morphology of the epithelial cells. The change in the middle of the colon is between the changes in the upper and lower segments. The intestinal permeability of the CHL1 (-/-) type mice fed with DSS was significantly increased by the detection of intestinal permeability with FITC. The concentration of FITC at the end of the colon was the strongest, and the retention of the DSS-induced CHL1 (-/-)-type mouse did not change significantly as compared to the DSS-induced CHL1 (+/ +)-type mouse, and the DSS-induced upper end of the CHL1 (-/-)-type mouse colon, 4. ChL1 deletion increased the infiltration of inflammatory cells in the colon tissue in order to detect the immunological mechanism of CHL1 deletion on inflammatory bowel disease, DSS induced the fifth day and day 7 to detect the expression of peripheral blood neutrophils. Compared with the CHL1 (+/ +)-type mice fed with DSS, the number of peripheral neutrophils in the DSS-induced CHL1 (-/-)-type mouse model was not increased, indicating that the deletion of CHL1 did not promote the proliferation and differentiation of the central granulocytes in the peripheral blood of the mouse, However, the infiltration of neutrophils in the colon tissue of the mice is significantly increased, which is likely due to the absence of CHL1. In addition, in that colon tissue, the infiltration of the macrophages to the colon is also significantly increase. In conclusion, the first time in this study, the expression of CHL1 in the intestinal tissue was observed, and the expression of CHL1 in inflammatory bowel disease was significantly increased; after CHL1 deletion, the infiltration of inflammatory cells and the permeability of the intestinal tract were enhanced, and the occurrence of inflammatory bowel disease was increased. The above results suggest that CHL1 plays an important protective role in the occurrence of inflammatory bowel disease. The study provided a new way of thinking for the intervention of inflammatory bowel disease.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R574
本文編號：2508808
[Abstract]:Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is an inflammatory disease in the gastrointestinal tract, with severe pathological changes, poor prognosis and an unknown cause. The inflammation of the ulcerative colitis mainly occurs in the mucous membrane. The most important symptoms include diarrhea, colorectal bleeding, increased mucus, and abdominal pain. Crohn's disease is a chronic inflammation that can occur in the digestive tract from the mouth to the anus, mainly in the ileum, the cecum and the colon. In the occurrence of Crohn's disease, inflammation is penetrated from the mucosal layer of the intestinal tract to the serosa layer, with the characteristics of segmental asymmetry, and epithelial-like granuloma may be found on some patients. IBD is a high incidence in the European and American countries, but the prevalence of IBD is also increasing in Asia and South America, according to the latest study. The etiology of IBD is mainly related to the factors such as environment, immunity, and genetics. However, the mechanism of chronic inflammation in the intestine is not clear. In some view, the occurrence of chronic inflammation of the intestinal tract is related to the intestinal mucosal immune deficiency[28]. In recent years, it has been found that cell adhesion molecules play an important role in the development of intestinal inflammation. Several major cell adhesion molecules mediate the recruitment of lymphocytes, including the selection of the protein, the integrin, the calcium mucin and the immunoglobulin superfamily. L-selectin or P-selectin was used to capture the adherence of the white blood cells to the high-endothelial venules, and a strong adhesion was formed between the LFA-1 and the integrin by rolling, and the VCAM-1 and the MAdCAM-1 on the epithelial cells were firmly adhered to the total of 4-1 (VLA-4) integrin. In clinical, many drugs are achieved by inhibiting the binding of cell adhesion molecules (CAM) to the inflammatory cells. For example, to inhibit the formation of a strong adhesion of the bevacizumab between the babo4 and 1vcam, and to inhibit the formation of a firm-adhered monocytic bevacizumab in the h4-7-mAdCAM-1. CHL1 is a kind of nerve cell adhesion molecule (NCAM) which is widely expressed in human body. In the past study, it has been found that it plays an important role in the formation of axons of adult neural circuits, the growth and survival of neurons. On the other hand, CHL1 and the deletion of colorectal cancer (DCC) have similar domains. Studies have shown that the expression of CHL1 in the colon tissue of patients with colon cancer is reduced[8,9]. However, the relationship between CHL1 and inflammatory bowel disease is still lacking. The occurrence of inflammatory bowel disease is often accompanied by an increase in inflammatory factors in the body, as well as the infiltration of inflammatory cells on the intestinal mucosa epithelium. The infiltration of neutrophils plays a key role in the occurrence of ulcerative colitis, and is a key marker to measure the activity of the disease and the degree of inflammation. In the normal healthy tissue, the neutrophils are distributed in a small amount in the lamina propria, and with the inflammation, infiltration to the epithelial surface or the crypt of the colon is related to the degenerative changes of the crypt and the infiltrates of the crypt. The activity of IBD is related to the development of neutrophil infiltration and the disappearance of the crypt. Neutrophil is considered a potential pharmacological target in the treatment of the interference with IBD. In IBD, monocyte-derived macrophages tend to increase due to the increased inflammatory response, and macrophages are critical to maintaining a steady state in the gastrointestinal environment, while resisting the destruction of pathogens to protect the intestinal tract. The degree of macrophage infiltration is also a sign of the degree of inflammation. In this study, the effect of CHL1 deletion on the colon inflammation induced by DSS was discussed by using Dextran Sulfonate Sodidium (DSS), and the mechanism of the infiltration of neutrophils and macrophages on the inflammatory response and tissue injury of the colon was studied. The main results are as follows:1. In order to explore the relationship between the inflammatory bowel disease and the neuroadhesion molecule CHL1, the expression of CHL1 in the colon tissue of the mouse was up-regulated by inflammatory bowel disease, and the model of the classic DSS mouse inflammatory bowel disease was established. The expression of the CHL1 tissue in the colon tissue of the mouse was detected on Day 5, Day 7, and Day 9 of the DSS-induced inflammatory bowel disease. At the protein level, the expression of CHL1 increased from day 5 of the induction of inflammatory bowel disease, and the expression of CHL1 on Day 7 and Day 9 continued to increase. The expression of CHL1 mRNA was detected by real-time quantitative PCR (Q-PCR) at the level of transcription. From day 7 onwards, the expression of CHL1 at the mRNA level was significantly increased. in ord to further explore that relationship between CHL1 and inflammatory bowel disease, The CHL1 (+/ +) and CHL1 (-/-) mice were divided into four groups according to whether or not the DSS was fed, and an inflammatory bowel disease model was established. In comparison with DSS-induced CHL1 (+/ +)-type mice, DSS-induced CHL1 (-/-)-type mice were significantly reduced in the occurrence of inflammatory bowel disease, with a significant reduction in body weight from day 7 of stress, and a significant increase in the mortality of the CHL1 (-/-)-type mice induced by DSS on Day 9. The length of the colon of the CHL1 (-/-) type mouse induced by DSS was significantly shortened, and the infiltration of the inflammatory cells and the tissue damage were serious. The results indicated that the deletion of CHL1 aggravated the occurrence of inflammatory bowel disease.3. The deletion of CHL1 caused the change of the structure of the colon epithelial cells in the mice, and the changes of the morphology of the epithelial tissue of the colon of the mice were observed by increasing the permeability of the intestinal tract. It was found that the deletion of CHL1 could make the arrangement of the columnar epithelial cells of the colon of the mouse in close alignment to be loose, the volume of the cells increased obviously, and the goblet-like cells increased. After DSS stress, the arrangement of the epithelial cells of the DSS-induced CHL1 (+/ +)-type mice is still in order, while the columnar epithelial cells of the DSS-induced CHL1 (-/-)-type mice are in an obvious disorder. The changes of the upper segment of the colon of the CHL1 (-/-) type mouse were mainly the change of the cell morphology of the epithelial cells. The changes of the lower segment of the colon were dominated by the disorder of the cell morphology of the epithelial cells. The change in the middle of the colon is between the changes in the upper and lower segments. The intestinal permeability of the CHL1 (-/-) type mice fed with DSS was significantly increased by the detection of intestinal permeability with FITC. The concentration of FITC at the end of the colon was the strongest, and the retention of the DSS-induced CHL1 (-/-)-type mouse did not change significantly as compared to the DSS-induced CHL1 (+/ +)-type mouse, and the DSS-induced upper end of the CHL1 (-/-)-type mouse colon, 4. ChL1 deletion increased the infiltration of inflammatory cells in the colon tissue in order to detect the immunological mechanism of CHL1 deletion on inflammatory bowel disease, DSS induced the fifth day and day 7 to detect the expression of peripheral blood neutrophils. Compared with the CHL1 (+/ +)-type mice fed with DSS, the number of peripheral neutrophils in the DSS-induced CHL1 (-/-)-type mouse model was not increased, indicating that the deletion of CHL1 did not promote the proliferation and differentiation of the central granulocytes in the peripheral blood of the mouse, However, the infiltration of neutrophils in the colon tissue of the mice is significantly increased, which is likely due to the absence of CHL1. In addition, in that colon tissue, the infiltration of the macrophages to the colon is also significantly increase. In conclusion, the first time in this study, the expression of CHL1 in the intestinal tissue was observed, and the expression of CHL1 in inflammatory bowel disease was significantly increased; after CHL1 deletion, the infiltration of inflammatory cells and the permeability of the intestinal tract were enhanced, and the occurrence of inflammatory bowel disease was increased. The above results suggest that CHL1 plays an important protective role in the occurrence of inflammatory bowel disease. The study provided a new way of thinking for the intervention of inflammatory bowel disease.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R574
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