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In the central nervous system, gap junctions exist between neurons and glial cells. Among them, connexin 43 (Cx43) is one of the most abundant connexin proteins in the central nervous system,involved in the metabolic coupling of intercellular substance exchange and electrical coupling of electrical signaling. It plays an important role in regulating cell metabolism, homeostasis, and cell differentiation. After cerebral ischemia, the uncoupling of gap junctions and abnormal hemichannel activity cause a steady-state imbalance of the internal and external environment of the cells, eventually leading to brain tissue damage.Therefore, maintaining the normal function of Cx43 is essential for protecting brain tissue from neuronal damage induced by cerebral ischemia-reperfusion.
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AIM:To investigate the effect of Xingnaojing (XNJ) injection on the permeability of blood-brain barrier ( BBB) and zonula occludens-1 ( ZO-1) protein expression after global ischemia-reperfusion in rats.METHODS:Improved Pulsinelli four-vessel occlusion method was adopted to establish the global ischemia-reperfusion model in the rats. Male Wistar rats were randomly divided into sham group, model group, solvent group and XNJ group.The observations were conducted at the time points of 24 h, 48 h and 72 h after ischemia reperfusion.The water content of the brain tissues was determined by dry-wet weight method, while the Evans blue ( EB) content of brain tissue was detected by spectropho-tometry.The protein levels of ZO-1 in the cerebral cortex were analyzed by Western blot.RESULTS:The water contents in the brain tissues in model group, solvent group and XNJ group were significantly higher than those in sham group ( P<0.05) 24 h after ischemia reperfusion.However, the brain water contents in model group and solvent group were signifi-cantly higher than those in XNJ group and sham group (P<0.05) 48 h and 72 h after ischemia reperfusion.The EB con-tents in the brain tissues in model group, solvent group and XNJ group were entirely higher than that in sham group 24 h af-ter ischemia reperfusion (P<0.05).The EB contents in sham group and XNJ group were significantly lower than those in model group and solvent group 48 h and 72 h after ischemia reperfusion (P<0.05).The protein expression of ZO-1 in the rat cerebral cortex in model group, solvent group and XNJ group was significantly lower than that in sham group 24 h after ischemia-reperfusion (P<0.05).Similarly, 48 h and 72 h after ischemia reperfusion, ZO-1 protein level in the cortex in sham group and XNJ group was significantly higher than that in model group and solvent group (P<0.05).CONCLU-SION:At 48 h and 72 h after global ischemia-reperfusion, Xingnaojing injection play a protective role in blood-brain barri-er and this role may be associated with the increase in ZO-1 protein expression by Xingnaojing injection.
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Objective To investigate the effects of exogenous hydrogen sulfide on brain edema and injury and their mechanisms. Methods Sixty male SD rats were randomly divided into a sham operation group, an ischemia-reperfusion group, a 30 ppm hydrogen sulfide group, and a 60 ppm hydrogen sulfide group (n =15 in each group; 1 ppm =1 mg/L). A model of focal cerebral ischemia for 2 h and reperfusion for 24 h was induced by middle cerebral artery occlusion. The neurological scores were observed after 24 h cerebral ischemia-reperfusion. The cerebral infarction volume, the degree of brain edema, and the changes of blood-brain barrier permeability were measured. Western blotting was used to detect the expressions of occludin and zonula occludens-1 protein (ZO-1) in ischemic penumbra. Results Compared with the ischemia-reperfusion group, the neurological function scores in the 30 ppm and 60 ppm hydrogen sulfide group significantly increased in a dose-dependent manner (al P brain edema aleviated (al P < 0.05). The content of Evans blue in the ischemic brain tissue in the ischemia-reperfusion group increased significantly compare with the sham operation group (0.74 ±0.14 μg/100 mg vs. 0.19 ±0.06 μg/100 mg; P <0.05). The content of Evans blue in the brain tissue in the 30 ppm hydrogen sulfide group (0.55 ±0.10 μg/100 mg ) and the 60 ppm hydrogen sulfide group (0.35 ±0.08 μg/100 mg ) decreased significantly compared with the ischemia-reperfusion group (al P < 0.05), among them the 60 ppm hydrogen sulfide group was significantly lower than the 30 ppm hydrogen sulfide group (P <0.05). Western blot analysis showed that expression levels of occludin in penumbra (0.621% ±0.101% vs.0.787% ±0.087% vs.0.453% ± 0.127%; P <0.05) and ZO-1 (0.602% ±0.118% vs.0.778% ±0.805% vs.0.426% ±0.146; P <0.05) in the 30 ppm and 60 ppm hydrogen sulfide groups increased significantly compared with the ischemia-reperfusion group, among them, the expression levels of occludin and ZO-1 in the 60 ppm hydrogen sulfide group were significantly higher than those in the 30 ppm hydrogen sulfide group (al P < 0.05). Conclusions Inhalation of exogenous hydrogen sulfide can significantly attenuate brain edema after ischemia-reperfusion in a dose dependent manner, reduce infarct volume, and improve neurological function.Their mechanisms may be associated with inhibiting the downregulated expressions of occludin and ZO-1 and maintaining the integrity of the blood-brain barrier.
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Background : The expressions of osteopontin (OPN), zonula occludens-1 (ZO-1) and E-cadherin, known as cell adhesion-associated substances, were examined in adenoma and adenocarcinoma of the colon. The relationship of their expressions with clinicopathologic factors was examined to investigate the roles of these proteins in the development, invasion or metas- tasis of colon adenocarcinoma. Methods : The expressions of OPN, ZO-1, and E-cadherin were examined in 54 cases of adenoma and 67 cases of adenocarcinoma of the colon by immunohistochemical staining. Results : The expression of OPN in colon adenocarcinoma correlated with staging (p=0.012) and distant metastasis (p=0.021). The expression of ZO-1 was closely related with tumor cell differentiation (p<0.001), and the reduced expression of E-cadherin was associated with tumor cell differentiation (p=0.05) and lymph node metastasis (p<0.001). Co-expression of ZO-1 and E-cadherin was significantly associated with tumor cell differentiation, and the expressions of ZO-1 and E-cadherin were reduced or lost in all cases (5 cases) of poorly differentiated adenocarcinoma. Conclusions : Our data suggest that OPN is involved in the process of invasion and metastasis of colon adenocarcinoma, and ZO-1- and E-cadherin-mediated cell adhesion may play an important role in the differentiation of colon adenocarcinoma.