雷公藤红素缓解刀豆蛋白A诱导的小鼠急性肝损伤作用及其机制

将36只同一批次体重无明显差异的7周龄C57雄鼠随机分为6组,每组6只,即对照组,模型组,地塞米松(dexamethasone, DXM)组及雷公藤红素(celastrol, Cel)低、中、高剂量组(1.5、3、6 mg/kg),连续灌胃7 d后尾静脉注射20 mg/kg刀豆蛋白A(concanavalin A, ConA),地塞米松(0.5 mg/kg)于刀豆蛋白给药前1 h腹腔注射.注射8 h后处死小鼠,取其血清分别检测白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和丙氨酸氨基转移酶(ALT)及天冬氨酸转移酶(AST)的含量.取小鼠肝脾称重计算脏器系数,苏木精-伊红(HE)染色观察肝组织病理改变,用实时定量PCR法(RT-qPCR法)检测肝组织中相关基因mRNA的表达水平,流式细胞术检测脾脏中巨噬细胞的极化方向,从而研究雷公藤红素对刀豆蛋白A诱导的小鼠急性肝损伤的保护作用及其机制.结果显示:相较于正常组,模型组小鼠的肝组织明显发生急性肝炎,其小叶结构紊乱,肝细胞结构破坏,汇管区炎症细胞浸润,雷公藤...     

Synaptic potentiation onto habenula neurons in the learned helplessness model of depression

The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.