本文選題：潰瘍性結(jié)腸炎　切入點：翁連解毒湯　出處：《河北醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:潰瘍性結(jié)腸炎(ulcerative colitis,UC)是發(fā)生在直腸和結(jié)腸的、累及黏膜及黏膜下層的慢性非特異性炎癥性疾病,發(fā)病率高,且易復(fù)發(fā),病程較長。本實驗通過觀察翁連解毒湯方對潰瘍性結(jié)腸炎大鼠的一般狀態(tài)、疾病活動指數(shù)(DAI)評分、血清IL-17含量及結(jié)腸組織TLR2表達的影響,探討翁連解毒湯治療潰瘍性結(jié)腸炎的作用機制,為臨床應(yīng)用提供實驗依據(jù)。方法:將60只潔凈雄性健康Wistar大鼠根據(jù)隨機數(shù)字表隨機分為6組,每組10只,分別為空白對照組(NG)、模型組(MG)、西藥美沙拉嗪組(XG)、中藥高劑量組(HG)、中藥中劑量組(ZG)、中藥低劑量組(LG)�？瞻讓φ战M(NG)正常飼養(yǎng),其余5組大鼠均采用三硝基苯磺酸(TNBS)/乙醇聯(lián)合造模方法建立潰瘍性結(jié)腸炎大鼠模型。自造模后第4天,各組大鼠除NG、MG正常飼養(yǎng)外,余治療組大鼠除基礎(chǔ)飼養(yǎng)外合用藥物灌胃,其中XG組大鼠采取美沙拉嗪混懸液灌胃,HG、ZG和LG大鼠采用不同的濃度的翁連解毒湯灌胃治療。連續(xù)治療2周后,觀察大鼠在各個時期的精神狀態(tài)、飲食、被毛、糞便性狀、體重等一般狀態(tài)的變化并記錄,做出疾病活動指數(shù)評分表。治療結(jié)束后,各組大鼠禁食不禁水24小時,利多卡因麻醉大鼠取股動脈血,用雙抗體夾心ABC-ELLISA法檢測血清IL-17含量,解剖并取其肉眼觀察病變較重部位的結(jié)腸組織,常規(guī)石蠟包埋、切片、HE染色,檢測TLR2的表達情況。結(jié)果:1一般情況觀察:NG大鼠一般狀態(tài)良好,余組大鼠精神萎靡,反應(yīng)遲鈍,進食水量減少,體重下降,糞便稀薄夾雜粘液、膿血。藥物灌胃治療后各組大鼠精神狀態(tài)好轉(zhuǎn),進食量明顯增多,體重下降減慢,粘液、膿血便減少或消失,其中HG改善最明顯,ZG、XG改善無明顯差異,較HG略差,較LG較好。DAI評分結(jié)果提示:XG、HG、ZG、LG與MG相比較低,差異有統(tǒng)計學(xué)意義(P0.05);XG、ZG、LG與HG相比較高,差異有統(tǒng)計學(xué)意義(P0.05);XG與ZG無統(tǒng)計學(xué)意義(P0.05);XG、ZG與LG相比較低,差異有統(tǒng)計學(xué)意義(P0.05)。2結(jié)腸黏膜肉眼與病理學(xué)觀察肉眼觀察:NG大鼠上皮黏膜光滑完整。MG大鼠黏膜充血水腫糜爛面最明顯。HG大鼠黏膜較光滑,潰瘍面極少。XG和ZG大鼠黏膜欠光滑,可見較少的潰瘍面。LG大鼠黏膜組織輕度充血水腫,潰瘍灶較多。組織病理學(xué)觀察:NG大鼠黏膜光滑,腺體結(jié)構(gòu)排列規(guī)則。MG大鼠黏膜粗糙,可見多發(fā)、彌漫性糜爛或潰瘍面,局部腺體破壞最明顯,可見大量炎性細胞浸潤。HG組黏膜較光滑完整,新生腺體最多。XG和ZG大鼠黏膜欠光滑,可見少許炎性細胞浸潤,潰瘍面較少。LG大鼠黏膜組織輕度充血水腫,遺留潰瘍灶較多,少數(shù)處于愈合期,潰瘍面及邊緣覆于少量新生腺體,見附圖Fig.1-Fig.12。3指標(biāo)檢測IL-17含量比較:MG、XG、HG、ZG、LG與NG相比含量較高,差異有統(tǒng)計學(xué)意義(P0.05);HG、XG、ZG、LG與MG相比,含量較低,差異有統(tǒng)計學(xué)意義(P0.05);XG、ZG、LG與HG相比含量較高,差異有統(tǒng)計學(xué)意義(P0.05);XG、ZG與LG相比含量較低,且差異有統(tǒng)計學(xué)意義(P0.05);XG與ZG相比較,差異無統(tǒng)計學(xué)意義(P0.05)。TLR2表達比較:MG、XG、HG、ZG、LG與NG相比表達較高,差異有統(tǒng)計學(xué)意義(P0.05);XG、HG、ZG、LG與MG相比,表達較低,差異具有統(tǒng)計學(xué)意義(P0.05);HG較XG、ZG、LG相比,表達較低,差異有統(tǒng)計學(xué)意義(P0.05);ZG、XG與LG相比,表達較低,差異有統(tǒng)計學(xué)意義(P0.05);XG與ZG相比較,差異無統(tǒng)計學(xué)意義(P0.05)。結(jié)論:翁連解毒湯能夠改善潰瘍性結(jié)腸炎大鼠的一般情況并且能夠修復(fù)損傷的黏膜,降低DAI評分,并呈現(xiàn)一定的量-效關(guān)系,其特點為隨著中藥濃度的升高而療效增加,其作用機制可能通過降低TLR2的表達、減少IL-17的含量,從而阻斷炎癥反應(yīng),減少炎性細胞浸潤,刺激局部組織再生與修復(fù),達到愈合潰瘍面的作用。
[Abstract]:Objective: ulcerative colitis (ulcerative colitis, UC) occurred in the rectum and colon, involving the mucosa and submucosa of chronic non-specific inflammatory disease, high incidence and recurrence, longer duration. This experiment through the observation of Weng Jiedu Decoction on even ulcerative colitis rats general state, disease the activity index (DAI) score, the expression of TLR2 IL-17 in serum and colon tissue, to explore the mechanism of treating ulcerative colitis even Weng Jiedu Decoction, provide experimental basis for clinical application. Methods: 60 clean healthy male Wistar rats according to randomly divided into 6 groups, 10 rats in each group, respectively. For the control group (NG), model group (MG), western medicine group (XG) the beauty of salad, high dose of Chinese medicine group (HG), Chinese medicine dose group (ZG), low dose of Chinese medicine group (LG). The blank control group (NG) of normal feeding, the remaining 5 groups of rats were three nitrobenzene sulfonic acid (TNBS) / ethanol combined modeling method to establish the rat model of ulcerative colitis. The model was made after fourth days, the rats in NG, MG more than normal feeding, the rats in the treatment group in addition to the basic drug fed by gavage, the rats in the XG group to take the salad suspension gavage, HG ZG, and LG of rats with different concentrations of Weng even Jiedu Decoction by gavage. After 2 weeks of continuous treatment, rats were observed in each period of the mental state, diet, hair, stool, weight change etc. the general state and make record, disease activity index score. After treatment, fasting rats can not help water for 24 hours, lidocaine anesthesia rats from femoral artery blood, by double antibody sandwich ABC-ELLISA assay of serum IL-17 content, and the anatomy of the colon tissue observed lesions heavier parts, paraffin embedded sections, HE staining to detect the expression of TLR2. Results: 1 the general situation Observe the general condition of rats: NG rats were more than good, apathetic, unresponsive, eating less water, weight loss, thin stool with mucus, pus and blood. Drug irrigation improved mental state of rats after the treatment of stomach, food intake increased significantly, decreased body weight decreased, mucous pus blood decreased or disappeared. The most obvious improvement in HG, ZG, XG improvement had no significant difference compared with HG slightly worse than LG better.DAI score showed: XG, HG, ZG, LG and MG are relatively low, the difference was statistically significant (P0.05); XG, ZG, LG and HG are relatively high, the difference was statistically significant (P0.05); XG and ZG had no statistical significance (P0.05); XG, ZG and LG are relatively low, the difference was statistically significant (P0.05) were observed with naked eye and eye pathology of.2 in colonic mucosa of NG rats mucosa smooth and complete the most obvious.MG rat mucosal edema.HG rat mucosal erosion surface was relatively smooth. The ulcer rarely.XG and ZG rats Mucosa less smooth, less visible mucosa ulcer.LG rats with mild hyperemia and edema, ulcer more. Histopathological observation: mucosal NG rats smooth, glandular structures arranged in mucosa of.MG rats of rough rules, there are multiple, diffuse erosion or ulcer, local glands broken the most obvious, visible inflammatory infiltration of inflammatory cells in group.HG mucosa is smooth and complete, the new maximum of.XG and ZG in rat glandular mucosa was not smooth, there is little inflammatory cell infiltration in mucosa of rats with ulcer less.LG mild hyperemia and edema, ulcer left more, a few in the healing period, the ulcer surface and edge to cover a few new glands, see figure Fig.1-Fig.12.3 index to detect the content of IL-17: MG, XG, compared with HG, ZG, LG were higher compared with NG, the difference was statistically significant (P0.05); HG, XG, ZG, LG compared with MG, content is low, the difference was statistically significant (P0.05); XG, ZG, LG and HG were compared 杈冮珮,宸紓鏈夌粺璁″鎰忎箟(P0.05);XG,ZG涓嶭G鐩告瘮鍚噺杈冧綆,涓斿樊寮傛湁緇熻瀛︽剰涔，

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