Extracellular signal-regulated kinase pathways may mediate the protective effect of electrical stimulation of the paraventricular nucleus against ischaemia-reperfusion injury of the gastric mucosa
Extracellular signal-regulated kinase pathways may mediate the protective effect of electrical stimulation of the paraventricular nucleus against ischaemia-reperfusion injury of the gastric mucosa
复制标题
DOI：
10.1111/j.1440-1681.2007.04652.x
复制
发表时间：
2007-08-01
影响因子：
2.9
通讯作者：
Zhang, Jian-Fu
中科院分区：
文献类型：
--
作者：
Zhang, Yong-Mei;Wei, Er-Qing;Zhang, Jian-Fu
1.本研究旨在阐明细胞外信号调节激酶(ERK)通路在电刺激室旁核(PVN)对胃缺血再灌注损伤(GI/RI)诱导的细胞凋亡和增殖中的作用。为探讨电刺激下丘脑室旁核(PVN)对缺血再灌注(I/R)后胃粘膜细胞凋亡和增殖的影响，采用夹闭腹主动脉30min，再灌流30min或1、3、6h的GI/RI模型，采用免疫组织化学和免疫印迹方法检测电刺激PVN后不同时间ERKs的表达、活化和分布及其下游细胞因子Bcl2和Bax的动态变化。电刺激PVN可明显减轻再灌注30min、1h和3h的GI/RI。再灌流30min后，电刺激可减少胃粘膜细胞凋亡，促进胃粘膜增殖，促进磷酸化(P)-ERK1/2的表达和活化。电刺激使再灌注30min、1h和3h的Bcl2表达增加，Bax表达降低。相反，在I/R加或不加电刺激PVN的大鼠再灌注1h，特异性的上游丝裂原活化蛋白激酶抑制剂PD98059抑制ERK1/2的活性也有类似的效果。PD98059可加重胃粘膜损伤，增加细胞凋亡率，减少胃粘膜细胞增殖，降低p-ERK1/2和Bcl一2的表达和活性，增加Bax的表达。这些结果表明，PVN对GI/RI具有保护作用，这种保护作用可能与抑制胃粘膜细胞凋亡和促进细胞增殖有关，可能是通过激活ERK通路实现的。
1. The aim of the present study was to elucidate the role of the extracellular signal-regulated kinase (ERK) pathway in mediating the effects of electrical stimulation of the paraventricular nucleus (PVN) on apoptosis and proliferation induced by gastric ischaemia-reperfusion injury (GI/RI).2. To investigate the effects of electrical stimulation of the hypothalamic PVN on gastric mucosal apoptosis and proliferation in response to ischaemia-reperfusion (I/R), we used a GI/RI model by clamping the coeliac artery for 30 min and then reperfusing the artery for 30 min or 1, 3 or 6 h. We used immunohistochemistry and western blotting to investigate the expression, activation and distribution of ERKs and the dynamic changes in their downstream cellular factors Bcl-2 and Bax at different times subsequent to electrical stimulation of the PVN in the I/R-injured gastric mucosa.3. Electrical stimulation of the PVN markedly attenuated GI/RI at 30 min and 1 and 3 h after reperfusion. Electrical stimulation decreased gastric mucosal apoptosis, increased gastric mucosal proliferation and promoted the expression and activation of phosphorylated (p)-ERK1/2 30 min after reperfusion. Electrical stimulation increased the expression of Bcl-2 and decreased the expression of Bax at 30 min and 1 and 3 h after reperfusion. In contrast, inhibition of ERK1/2 activity by the specific upstream mitogen-activated protein kinase kinase inhibitor PD98059 produced similar effects at 1 h after reperfusion in rats subjected to I/R with or without electrical stimulation of the PVN. Administration of PD98059 aggravated gastric mucosal injury, increased apoptosis, decreased proliferation in gastric mucosal cells, decreased the expression and activity of p-ERK1/2 and Bcl-2 expression and increased Bax expression.4. These results indicate that the PVN protects against GI/RI and that this protection is associated with the inhibition of cellular apoptosis and the promotion of proliferation in the gastric mucosa, probably by activating the ERK pathway.