双联抗血小板药物致胃肠道损伤机制的动物实验研究
发布时间：2018-08-29 12:53
【摘要】：目的 观察阿司匹林、氯吡格雷、阿司匹林联合氯吡格雷(双联抗血小板药物)对大鼠胃、小肠损伤的情况,并探讨不同实验组胃、小肠损伤与炎症因子表达的关系,为将来防治抗血小板药物相关性的胃肠道损伤,提供实验依据。 方法 将80只SD大鼠(6-7周龄,体重200-220g,雄性远交群Sprague Dawley)随机分成阴性对照组、阿司匹林组、氯吡格雷组、阿司匹林联合氯吡格雷组,每组20只；每天分别给予生理盐水、阿司匹林10.41mg/kg、氯吡格雷组7.81mg/kg、阿司匹林10.41mg/kg联合氯吡格雷组7.81mg/kg灌胃,共14天。所有大鼠于末次给药后手术,对胃和小肠进行大体损伤评分,将胃、小肠组织HE染色后进行病理组织学损伤评分,并通过免疫组化方法分析炎性因子TNF-α、 IL-1β的表达情况。 结果 1、大鼠胃、小肠大体损伤评分结果：按Guth标准胃损伤指数,阴性对照组为0.000±0.000,阿司匹林组为3.550±0.822,氯吡格雷组为2.200±0.443,阿司匹林联合氯吡格雷组为4.550±0.915,F=57.393,P0.05,结果有统计学意义。根据Reuter评分标准小肠损伤指数,阴性对照组为0.000±0.000；阿司匹林组为2.950±0.710；氯吡格雷组为1.600±0.595；阿司匹林联合氯吡格雷组为3.400±0.950,F=46.566,P0.05,结果有统计学意义。 2、大鼠胃、小肠粘膜形态学损伤评分结果：根据光镜下黏膜损伤的程度判断标准,对各组胃粘膜损伤分级评分,阴性对照组胃黏膜损伤以0级为主占100%,阿司匹林组损伤为以Ⅱ级和Ⅲ-Ⅳ级损伤为主,占80%,氯吡格雷组以Ⅰ级和Ⅱ级为主,共占约80%,阿司匹林联合氯吡格雷组以Ⅱ-Ⅳ级损伤为主,共占95%,P0.05,结果有统计学意义。按照Chiu氏评分标准对小肠粘膜损伤评分,对照组为0.000±0.000,阿司匹林组为2.030+1.114,氯吡格雷组为1.089±0.792,阿司匹林联合氯吡格雷组为3.550±1.451。F=42.833,P0.05,结果有统计学意义。 3、大鼠胃和小肠炎症因子TNF-α、IL-1β的表达情况： 胃组织中TNF-α表达情况,阴性对照组以阴性(-)／(±)表达为主,占90%,阿司匹林组损伤为以阳性表达(++)为主占40%,并有20%的强阳性(+++)表达,氯吡格雷组以弱阳性(+)表达为主,共占约55%,阿司匹林联合氯吡格雷组以强阳性(+++)表达为主,共占65%,P0.05,结果有统计学意义。胃组织中IL-1β表达情况,阴性对照组以阴性(-)/(±)表达为主,占95%,阿司匹林组损伤为以阳性表达(++)为主占45%,并有30%的强阳性(+++)表达,氯吡格雷组以弱阳性(+)表达为主,共占约50%,阿司匹林联合氯吡格雷组以强阳性(+++)表达为主,共占70%,P0.05,结果有统计学意义。 小肠组织中TNF-α表达情况,阴性对照组以阴性(-)/(±)表达为主,占95%,阿司匹林组损伤为以阳性表达(++)为主占40%,并有25%的强阳性(+++)表达,氯吡格雷组以弱阳性(+)和阳性(++)表达为主,共占约85%,阿司匹林联合氯吡格雷组以强阳性(+++)表达为主,共占60%,P0.05,结果有统计学意义。小肠组织中IL-1β表达情况,阴性对照组以阴性(-)/(±)表达为主,占95%,阿司匹林组损伤为以阳性表达(++)为主占45%,并有30%的强阳性(+++)表达,氯吡格雷组以弱阳性(+)表达为主,共占约50%,阿司匹林联合氯吡格雷组以强阳性(+++)表达为主,共占70%,P0.05,结果有统计学意义。 结论 1、抗血小板药物可导致大鼠胃粘膜损伤,单用阿司匹林对大鼠胃肠粘膜损伤较单用氯毗格雷略重,阿司匹林联合氯吡格雷用药对胃粘膜的损伤最重。 2、抗血小板药物可导致大鼠小肠粘膜损伤,单用阿司匹林对大鼠小肠粘膜损伤较单用氯吡格雷略重,阿司匹林联合氯吡格雷用药对小肠粘膜的损伤最重。 3、炎症反应因子TNF-α、IL-1β在抗血小板药物致大鼠损伤的胃及小肠粘膜中均有高表达,这说明炎症反应在抗血小板药物导致大鼠胃、小肠损伤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.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965
[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.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965
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