發(fā)布時(shí)間：2018-08-29 12:53

【摘要】：目的 觀察阿司匹林、氯吡格雷、阿司匹林聯(lián)合氯吡格雷(雙聯(lián)抗血小板藥物)對(duì)大鼠胃、小腸損傷的情況,并探討不同實(shí)驗(yàn)組胃、小腸損傷與炎癥因子表達(dá)的關(guān)系,為將來防治抗血小板藥物相關(guān)性的胃腸道損傷,提供實(shí)驗(yàn)依據(jù)。 方法 將80只SD大鼠(6-7周齡,體重200-220g,雄性遠(yuǎn)交群Sprague Dawley)隨機(jī)分成陰性對(duì)照組、阿司匹林組、氯吡格雷組、阿司匹林聯(lián)合氯吡格雷組,每組20只；每天分別給予生理鹽水、阿司匹林10.41mg/kg、氯吡格雷組7.81mg/kg、阿司匹林10.41mg/kg聯(lián)合氯吡格雷組7.81mg/kg灌胃,共14天。所有大鼠于末次給藥后手術(shù),對(duì)胃和小腸進(jìn)行大體損傷評(píng)分,將胃、小腸組織HE染色后進(jìn)行病理組織學(xué)損傷評(píng)分,并通過免疫組化方法分析炎性因子TNF-α、 IL-1β的表達(dá)情況。 結(jié)果 1、大鼠胃、小腸大體損傷評(píng)分結(jié)果：按Guth標(biāo)準(zhǔn)胃損傷指數(shù),陰性對(duì)照組為0.000±0.000,阿司匹林組為3.550±0.822,氯吡格雷組為2.200±0.443,阿司匹林聯(lián)合氯吡格雷組為4.550±0.915,F=57.393,P0.05,結(jié)果有統(tǒng)計(jì)學(xué)意義。根據(jù)Reuter評(píng)分標(biāo)準(zhǔn)小腸損傷指數(shù),陰性對(duì)照組為0.000±0.000；阿司匹林組為2.950±0.710；氯吡格雷組為1.600±0.595；阿司匹林聯(lián)合氯吡格雷組為3.400±0.950,F=46.566,P0.05,結(jié)果有統(tǒng)計(jì)學(xué)意義。 2、大鼠胃、小腸粘膜形態(tài)學(xué)損傷評(píng)分結(jié)果：根據(jù)光鏡下黏膜損傷的程度判斷標(biāo)準(zhǔn),對(duì)各組胃粘膜損傷分級(jí)評(píng)分,陰性對(duì)照組胃黏膜損傷以0級(jí)為主占100%,阿司匹林組損傷為以Ⅱ級(jí)和Ⅲ-Ⅳ級(jí)損傷為主,占80%,氯吡格雷組以Ⅰ級(jí)和Ⅱ級(jí)為主,共占約80%,阿司匹林聯(lián)合氯吡格雷組以Ⅱ-Ⅳ級(jí)損傷為主,共占95%,P0.05,結(jié)果有統(tǒng)計(jì)學(xué)意義。按照Chiu氏評(píng)分標(biāo)準(zhǔn)對(duì)小腸粘膜損傷評(píng)分,對(duì)照組為0.000±0.000,阿司匹林組為2.030+1.114,氯吡格雷組為1.089±0.792,阿司匹林聯(lián)合氯吡格雷組為3.550±1.451。F=42.833,P0.05,結(jié)果有統(tǒng)計(jì)學(xué)意義。 3、大鼠胃和小腸炎癥因子TNF-α、IL-1β的表達(dá)情況： 胃組織中TNF-α表達(dá)情況,陰性對(duì)照組以陰性(-)／(±)表達(dá)為主,占90%,阿司匹林組損傷為以陽性表達(dá)(++)為主占40%,并有20%的強(qiáng)陽性(+++)表達(dá),氯吡格雷組以弱陽性(+)表達(dá)為主,共占約55%,阿司匹林聯(lián)合氯吡格雷組以強(qiáng)陽性(+++)表達(dá)為主,共占65%,P0.05,結(jié)果有統(tǒng)計(jì)學(xué)意義。胃組織中IL-1β表達(dá)情況,陰性對(duì)照組以陰性(-)/(±)表達(dá)為主,占95%,阿司匹林組損傷為以陽性表達(dá)(++)為主占45%,并有30%的強(qiáng)陽性(+++)表達(dá),氯吡格雷組以弱陽性(+)表達(dá)為主,共占約50%,阿司匹林聯(lián)合氯吡格雷組以強(qiáng)陽性(+++)表達(dá)為主,共占70%,P0.05,結(jié)果有統(tǒng)計(jì)學(xué)意義。 小腸組織中TNF-α表達(dá)情況,陰性對(duì)照組以陰性(-)/(±)表達(dá)為主,占95%,阿司匹林組損傷為以陽性表達(dá)(++)為主占40%,并有25%的強(qiáng)陽性(+++)表達(dá),氯吡格雷組以弱陽性(+)和陽性(++)表達(dá)為主,共占約85%,阿司匹林聯(lián)合氯吡格雷組以強(qiáng)陽性(+++)表達(dá)為主,共占60%,P0.05,結(jié)果有統(tǒng)計(jì)學(xué)意義。小腸組織中IL-1β表達(dá)情況,陰性對(duì)照組以陰性(-)/(±)表達(dá)為主,占95%,阿司匹林組損傷為以陽性表達(dá)(++)為主占45%,并有30%的強(qiáng)陽性(+++)表達(dá),氯吡格雷組以弱陽性(+)表達(dá)為主,共占約50%,阿司匹林聯(lián)合氯吡格雷組以強(qiáng)陽性(+++)表達(dá)為主,共占70%,P0.05,結(jié)果有統(tǒng)計(jì)學(xué)意義。 結(jié)論 1、抗血小板藥物可導(dǎo)致大鼠胃粘膜損傷,單用阿司匹林對(duì)大鼠胃腸粘膜損傷較單用氯毗格雷略重,阿司匹林聯(lián)合氯吡格雷用藥對(duì)胃粘膜的損傷最重。 2、抗血小板藥物可導(dǎo)致大鼠小腸粘膜損傷,單用阿司匹林對(duì)大鼠小腸粘膜損傷較單用氯吡格雷略重,阿司匹林聯(lián)合氯吡格雷用藥對(duì)小腸粘膜的損傷最重。 3、炎癥反應(yīng)因子TNF-α、IL-1β在抗血小板藥物致大鼠損傷的胃及小腸粘膜中均有高表達(dá),這說明炎癥反應(yīng)在抗血小板藥物導(dǎo)致大鼠胃、小腸損傷中可能起了重要作用。
[Abstract]:objective
To observe the effects of aspirin, clopidogrel, aspirin and clopidogrel on gastrointestinal injury in rats, and to explore the relationship between gastrointestinal injury and inflammatory factors expression in different experimental groups.
Method
Eighty SD rats (6-7 weeks old, body weight 200-220 g, male outcrossing group Sprague Dawley) were randomly divided into negative control group, aspirin group, clopidogrel group, aspirin combined with clopidogrel group, 20 rats in each group; normal saline, aspirin 10.41 mg/kg, clopidogrel group 7.81 mg/kg, aspirin 10.41 mg/kg and clopidogrel group were given daily respectively. All the rats were operated on after the last administration. The gastrointestinal lesions were scored. The histopathological lesions were scored after HE staining of gastrointestinal and gastrointestinal tissues. The expressions of inflammatory factors TNF-a and IL-1 beta were analyzed by immunohistochemistry.
Result
1. Rat gastrointestinal gross injury score: According to Guth standard gastric injury index, the negative control group was 0.000 + 0.000, aspirin group was 3.550 + 0.822, clopidogrel group was 2.200 + 0.443, aspirin combined with clopidogrel group was 4.550 + 0.915, F = 57.393, P 0.05, the results were statistically significant. The negative control group was 0.000 + 0.000, aspirin group was 2.950 + 0.710, clopidogrel group was 1.600 + 0.595, aspirin combined with clopidogrel group was 3.400 + 0.950, F = 46.566, P 0.05, the results were statistically significant.
2. Rat gastric and small intestinal mucosal morphological injury score results: According to the degree of mucosal injury under light microscopy judgment criteria, the grading of gastric mucosal injury in each group, negative control group of gastric mucosal injury to 0 mainly accounted for 100%, aspirin group of injury to II and III-IV mainly, accounting for 80%, clopidogrel group to I and II mainly. The results were statistically significant. According to Chiu's score, the intestinal mucosal injury score of the control group was 0.000 + 0.000, aspirin group was 2.030 + 1.114, clopidogrel group was 1.089 + 0.792, aspirin combined with clopidogrel group was 3.550 + 1.45. 1.F=42.833, P0.05, the results were statistically significant.
3, the expression of inflammatory factors TNF- and IL-1 in stomach and small intestine of rats:
The expression of TNF-alpha in gastric tissue was mainly negative (-)/ (+) in negative control group (90%), positive (++) in aspirin group (40%) and strong (+++) in aspirin group (20%). Weak (+) in clopidogrel group (55%) and strong (++++) in aspirin combined with clopidogrel group (50%). 65%, P 0.05, the results were statistically significant. The expression of IL-1 beta in gastric tissues was mainly negative (-)/(+) in negative control group (95%), positive (++) in aspirin group (45%) and strong (+++) in 30% respectively. Weak (+) in clopidogrel group (50%) and aspirin combined with clopidogrel group (50%). Strong positive (+ + +) expression was the main factor, accounting for 70%, P0.05, and the results were statistically significant.
The expression of TNF-a was mainly negative (-)/(+) in the negative control group (95%), positive (++) in the aspirin group (40%) and strong (+++) in the aspirin group (25%), weak (+) and positive (+++) in the clopidogrel group (85%), and strong (++++) in the aspirin plus clopidogrel group (85%). The expression of IL-1 beta was mainly negative (-)/(+) in the negative control group (95%), positive (++) in the aspirin group (45%), and strong (++) in 30% of the aspirin group (30%), and weak (+) in the clopidogrel group (50%). The clopidogrel group was mainly strongly positive (+ + +), accounting for 70%, P0.05, the result was statistically significant.
conclusion
1. Antiplatelet drugs can cause gastric mucosal injury in rats. The gastrointestinal mucosal injury in rats treated with aspirin alone is slightly more serious than that of clopidogrel alone. The gastric mucosal injury in rats treated with aspirin combined with clopidogrel is the most serious.
2. Antiplatelet drugs can cause small intestinal mucosal damage in rats. Aspirin alone can cause slightly more serious damage to small intestinal mucosa than clopidogrel alone. Aspirin combined with clopidogrel has the most serious damage to small intestinal mucosa.
3. The expression of TNF-a and IL-1 beta in gastric and intestinal mucosa of rats with antiplatelet drug-induced injury showed that inflammatory reaction may play an important role in the gastrointestinal injury induced by antiplatelet drugs.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R965

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