下丘脑瘦素对大鼠胃运动的作用

The effect of the hypothalamic leptin on gastric motility in rats

目的:观察下丘脑外侧区(LH)及腹内侧区(VMH)微量注射瘦素对大鼠胃运动的作用。方法:应用慢性植入应力传感器记录清醒大鼠胃体和胃窦运动,颈外静脉插管取血样品,血清瘦素用放射免疫分析法(RIA)测定。采用不锈钢管插入LH及VMH,供注射瘦素用。结果:大鼠胃运动类型:空腹胃体与胃窦出现典型的消化间期移行性复合运动(MMC),分Ⅰ、Ⅱ、Ⅲ、Ⅳ时相,其Ⅲ相高振幅收缩波可从胃体传至胃窦;下丘脑注射瘦素对胃运动的作用:下丘脑LH和VMH注射0.3、0.6、1.2μg/2μl瘦素均明显抑制大鼠胃体和胃窦MMCⅢ相收缩运动(均P<0.01),呈剂量反应效应。VMH与LH瘦素两者对胃运动抑制作用比较,VMH瘦素对MMCⅢ相收缩活动的抑制作用强于LH(P<0.05);下丘脑注射瘦素对外周瘦素影响:当给LH和VMH注射瘦素时外周血中瘦素浓度上升,与胃运动抑制同步。LH与VMH注射瘦素分别使血清瘦素较对照组增加(38.21±9.42)%(P<0.05)和(54.25±11.37)%(P<0.01);迷走神经和拮抗剂作用:切断膈下迷走神经,阿托品及胆囊收缩素A(CCK-A)受体拮抗剂loxiglumide均可阻断下丘脑瘦素对胃运动的抑制效应及外周释放瘦素的作用。结论:下丘脑瘦素对胃运动有持续性抑制作用,其作用可能通过迷走-胆碱能神经及CCK-A受体介导。

Objective To observe the effect of leptin microinjection in lateral hypothalamus （LH） and ventromedial hypothalamus （VMH） on gastric motility in rats. Methods Strain gauges were implanted into the serosa of antrum and corpus in the conscious Wister rats to record the gastric motility. Cannula was inserted into the external jugular vein for blood samples. Serum leptin level was measured by radioimmunoassay （RIA）. Stainless steel cannula was inserted in LH and VMH for leptin microinjection. Results Typical migrating motor complex （MMC）： typical interdigestive with phase Ⅰ, Ⅱ, Ⅲ and IV was recorded in the antrum and corpus of fast rats. The high amplitude waves in phase Ⅲ could migrate from corpus to antrum. The effect of leptin microinjection in hypothalamus on gastric motility： the injection of leptin of 0.3, 0.6 and 1.2 μg/2μl inhibited contractions in phase Ⅲ of antrum and corpus of rats significantly （P〈0.01） in a dose depen- dent manner. The inhibitive effect of the leptin microinjection in VMH on phase m of MMC was much stronger than the microinjection in LH （P〈0.05）. The effect of leptin microinjection in hypothalamus on serum leptin： serum leptin concentration grew up at the same time of gastric motility inhibition when the leptin was injected in LH and VMH. Serum leptin increased by （38.21±9.42） % （P〈0.05） and （54.25±11.37） % （P〈0.01） when the leptin was injected in LH and VMH, respectively. The effect of vagus nerves and antagonists： cutting off subphrenic vagus nerves, atropine or loxiglumide could block the effect of leptin microinjeetion in hypothalamus on gastric motility and peripheral leptin release. Conelutsions Leptin in hypothalamus might have a continuous inhibitive effect on gastric motility. This effect of leptin was mediated by vagns-cholinergic pathway and CCK-A receptor.