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Effect and Mechanism of Gastric Mucosa in Rats Induced by Clopidogrel Combine Aspirin

Author: ZhangQiuZuo
Tutor: WangBangMao
School: Tianjin Medical University
Course: Internal Medicine
Keywords: Clopidogrel Aspirin Gastric mucosal injury Tumor necrosis factor -α Vascular endothelial growth factor
CLC: R96
Type: Master's thesis
Year: 2011
Downloads: 35
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Abstract

Objective To observe clopidogrel clopidogrel aspirin on gastric mucosal and morphological changes in the further understanding of the pathophysiological changes its cause injury process. Materials and Methods clean male SD rats 192, weight (200g ± 10) g. Randomly divided into a control group, clopidogrel, aspirin, and clopidogrel in combination with aspirin group (n = 48), respectively to normal saline, clopidogrel (7.81mg/kg.d), aspirin (10.41mg/kg, for. d), clopidogrel in combination with aspirin orally for 28 days. The four groups of rats were administered before and after the administration of 3d, 7d, 14d, 21d, 28d according to the different time points rats were sacrificed and stomachs were observed. The ulcer index measured Guth Act; the ordinary pathological histology determine light the extent of mucosal injury; immunohistochemical determination of gastric epithelial cells and endothelial cells intracytoplasmic TNF-α, VEGF expression. Mucosa general change in rats after clopidogrel orally 3d mucosal surface gradually scattered punctate erosion, bleeding, 7d damage reached a peak difference (P lt; 0.05) compared with the control group and before treatment, damage. Experimental group, low-dose aspirin orally 3d mucosal surface gradually scattered punctate erosion, bleeding, 14d injury reached a peak difference (P lt; 0.01) compared with the control group and before treatment, damage. Clopidogrel combined with aspirin orally 3d mucosal surface gradually scattered punctate erosion, bleeding, 14d injury reached a peak difference (P lt; 0.01) compared with the control group and before treatment, damage. The damage index after taking the aspirin group compared with clopidogrel group compared the difference was statistically significant (P lt; 0.01), damage index after taking the clopidogrel plus aspirin group compared with aspirin, and clopidogrel group compared the difference was significant ( P lt; 0.01). 2. Ordinary Histopathological observation structural integrity of the control group rat gastric mucosa, occasionally mucosal epithelial defect. The clopidogrel group most of the rat gastric mucosa grade Ⅰ ~ Ⅱ damage handful of grade Ⅲ injury. The aspirin group most of the rat gastric mucosa grade Ⅰ ~ Ⅱ damage grade Ⅲ injury. Clopidogrel aspirin group, part Ⅰ ~ Ⅱ grade of injury, most grade Ⅲ ~ Ⅳ injury, the experimental and control groups overall comparison was statistically significant (P lt; 0.01), can be considered groups stomach mucosal histological damage to the extent there is a difference. Immunohistochemistry of TNF-α, VEGF expression quantitative results show the different time points and the control group in each experimental group drug or medication compared, TNF-α obviously was expressed at high levels, there were significant differences (P lt; 0.05). The clopidogrel group TNF-α after administration 3d begin to express 7d positive cells reached a peak and begin to decline, 14d; of TNF-α and damage index was positively correlated (rs = 0.691, P lt; 0.01). Aspirin group TNF-α expression after administration 3d the 14d reached a peak of number of positive cells began to decline, 21d; TNF-α and damage index was positively correlated (rs = 0.704, P lt; 0.01). Clopidogrel plus aspirin group TNF-α expression after administration 3d the 14d reached a peak of number of positive cells began to decline, 21d; TNF-α and damage index was positively correlated (rs = 0.732, P lt; 0.01). TNF-α qualitative results show that the overall comparison in each experimental group and the control group was statistically significant (P lt; 0.01) that mucosal TNF-α qualitative expression differences. The quantitative results show the different time points in each experimental group after treatment with the control group or medication before VEGF levels there is a significant difference (P lt; 0.05). Clopidogrel group with a certain expression levels of VEGF before treatment, after treatment, the expression rapidly down, 3d expression that is up to the trough, than before treatment and control group were significantly different (P lt; 0.01), 7d start positive cells gradually picked up, but to 28d is still lower than the control group (P lt; 0.05). Aspirin group quickly raised 3d VEGF expression after treatment than before treatment compared to the control group a significant difference (P lt; 0.05)), then the expression has declined, 7d, 14d positive cells in the control group compared to no significant difference (P gt; 0.05), 21d, 28d once again raised. Clopidogrel in combination with aspirin after the administration of VEGF 3d down differences (P lt; 0.05), compared with the control group and before treatment, and then gradually recovered, 21d, 28d with the control group and before treatment compared to no difference (P gt ; 0.05). VEGF qualitative results in each experimental group and the control group overall compared statistically significant (P lt; 0.01), can be considered mucosal VEGF qualitative expression exists difference. Conclusion conventional dose of clopidogrel can cause gastric mucosal injury in rats. The gastric mucosa VEGF expression in rats fed clopidogrel reduced, TNF-α expression increased, suggesting that this change may be involved in gastric mucosal damage. Conventional low-dose aspirin can cause gastric mucosal injury in rats, and compared with the conventional dose clopidogrel as the most important. TNF-α expression increased VEGF expression is first raised and then decreased again raised the change process. Change considerations aspirin caused by VEGF endothelial growth factor in rat gastric mucosa injury regulating self-protective reaction. Clopidogrel in combination with aspirin on gastric mucosal injury compared with clopidogrel or aspirin alone significantly increased the damage peak appears in the 14d fed drugs. Induced gastric mucosal injury in rats with reduced VEGF expression, TNF-α enhanced expression related. Clopidogrel-induced gastric mucosa injury mechanism, we speculate may be due to the reduction of VEGF reduced gastric mucosal blood flow, thus reduced mucosal protective factor, cause gastric mucosal damage and its repair delay. Specific mechanisms need to be further in-depth study

Effect and Mechanism of Gastric Mucosa in Rats Induced by Clopidogrel Combine Aspirin

Abstract

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