机构地区:[1]青岛大学医学院病理生理学教研室,山东青岛266021 [2]菏泽医学专科学校生理学教研室
出 处:《青岛大学医学院学报》2012年第5期381-383,387,共4页Acta Academiae Medicinae Qingdao Universitatis
基 金:国家自然科学基金项目(No.30470642;No.30670780;No.31071014;No.81100260;No.81070305);山东省科技攻关项目(No.2008GG10002006);山东省卫生厅项目(No.2007HZ026);青岛市科技局项目(11-2-3-3-(2)-nsh)
摘 要:目的观察链脲佐菌素(STZ)所致糖尿病大鼠下丘脑弓状核(Arc)胃牵张(GD)敏感神经元放电活动改变,探讨ghrelin对糖尿病大鼠下丘脑Arc GD敏感神经元放电活动的影响及机制。方法采用STZ腹腔注射诱导糖尿病大鼠模型。通过细胞外记录神经元单位放电方法,观察ghrelin及其受体阻断剂[D-Lys-3]-GHRP-6对糖尿病大鼠下丘脑Arc GD敏感神经元自发放电活动的影响。结果在正常大鼠,Arc记录到的98个GD敏感神经元中,64.3%为GD兴奋性(GD-E)神经元,35.7%为GD抑制性(GD-I)神经元。Arc注射ghrelin可兴奋73.0%的GD-E神经元,其放电频率显著增加(t=2.01,P<0.05);Arc注射ghrelin可抑制60.0%的GD-I神经元,其放电频率显著降低(t=4.49,P<0.01);ghrelin改变GD神经元放电效应可被[D-Lys-3]-GHRP-6阻断。在糖尿病大鼠,Arc记录到的66个GD敏感神经元中56.1%为GD-E神经元,43.9%为GD-I神经元。Arc注射ghrelin可兴奋35.1%的GD-E神经元,其放电频率显著增加(t=2.67,P<0.05);而Arc注射ghrelin可抑制72.4%的GD-I神经元,其放电频率显著降低(t=3.95,P<0.01)。与正常大鼠比较,糖尿病大鼠Arc GD敏感神经元中GD-E和GD-I的比例无显著改变(P>0.05),但ghrelin使GD-E神经元兴奋比率明显降低(χ2=3.86,P<0.05),放电频率平均增加率也显著下降(t=2.02,P<0.05)。与正常大鼠比较,ghrelin使GD-I神经元抑制比率和放电频率平均减少率均无显著改变(P>0.05)。结论 ghrelin参与糖尿病大鼠下丘脑Arc GD敏感神经元自发放电活动的调控,该作用可能是通过作用ghrelin受体而实现的。Objective To observe the changes of activity of gastric distention(GD) sensitive neurons of hypothalamic arcuate nucleus(Arc) in rat models with diabetes mellitus(DM),and to study the effects of ghrelin on GD neurons in hypothalamic arcuatus nucleus in the rats.Methods A rat model of DM was created by intraperitoneal injection of streptozotocin(STZ).The effects of ghrelin and [D-Lys-3]-GHRP-6 on GD sensitive neurons of Arc in DM rats were observed by recording extracellular potentials of single neurons.Results In normal rats,98 GD sensitivity neurons were recorded in Arc of normal rats,in which,64.3% were classified as GD-excitatory(GD-E) neurons,and 35.7% were GD-inhibitory(GD-I) neurons.Microinjection of ghrelin could excite 73.0% of GD-E neurons,and discharge frequency significantly increased(t=2.01,P〈0.05),and inhibite 60.0% of GD-I neurons,and lower their discharge frequency(t=4.49,P〈0.01).The effect of ghrelin could be blocked by antagonist of ghrelin-[D-Lys-3]-GHRP-6.In DM rats,66 GD sensitivity neurons recorded in Arc,in which,56.1% were GD-E,and 43.9% were GD-I.Microinjection of ghrelin could excite 35.1% GD-E neurons,and discharge frequency significantly increased(t=2.67,P〈0.05),and inhibit 72.4% of GD-I neurons,and discharge frequency reduced(t=3.95,P〈0.01).Compared with normal rats,the ratio between GD-E and GD-I neurons in Arc of diabetic rats was not significantly changed(P〈0.05),but ghrelin made neuronal excitation ratio of GD-E obviously reduce(χ2=3.86,P〈0.05),and the average increase rate of discharge frequency was also significantly decreased(t=2.02,P〈0.05),the inhibition ratio and discharge average reduction rate reduced by ghrelin were not significantly changed in GD-I neurons(P〈0.05).Conclusion The ghrelin of hippocampus Arc involves in regulation of spontaneous discharge activity of GD sensitive neurons in diabetic rats,which is likely to be realized through ghrelin receptor.
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