补骨脂抑制肝组织NF—κB活性治疗幼龄小鼠脂肪肝的机制研究(1)
[摘要] 探讨补骨脂对幼龄小鼠脂肪肝(NAFLD)的防治作用及机制。该实验采用高脂饮食建立幼龄小鼠NAFLD模型，给予补骨脂颗粒剂(低、高剂量)治疗5周后，检测血糖、血脂(TC，TG，LDL-C，HDL-C)、空腹胰岛素、肝功能(ALT，AST)水平，计算胰岛素抵抗指数(HOMA-IR)，观察肝组织形态学改变，检测肝脏甘油三酯(TG)含量、CD44蛋白表达，同时检测肝组织核因子κB(NF-κB)p65磷酸化(p-p65)及非磷酸化蛋白(p65)表达及其下游细胞因子(TNF-α，IL-8)水平。结果显示与模型组比较，补骨脂组HOMA-IR，ALT，AST，空腹血糖，血脂(TC，TG，LDL-C)，肝脏TG含量降低(P<0.01，P<0.05)，HDL-C水平升高(P<0.01，P<0.05)，肝细胞脂肪变性减轻，汇管区纤维组织增生及炎细胞浸润改善，肝脏CD44蛋白表达减少，肝组织TNF-α，IL-8水平、p-p65/p65明显下降(P<0.01)。高剂量组疗效优于低剂量组(P<0.01，P<0.05)。结果表明补骨脂对幼龄小鼠脂肪肝具有防治作用，还可调节其糖脂代谢紊乱、改善肝纤维化。其机制可能与下调NF-κB的活性抑制炎症反应有关。
, 百拇医药
[关键词] 非酒精性脂肪性肝病；补骨脂；炎症；核因子κB；幼龄小鼠
[Abstract] To investigate the mechanism and effect of Psoralea corylifolia(PC) in the treatment of NAFLD in juvenal mice. The NAFLD model in juvenal mice was established by feeding high-fat diet. Then PC herbal granules (at low and high dose) were administered for 5 weeks. Blood glucose (FBG， PG-1 h/2 h)， blood lipid (TC， TG， HDL-C， LDL-C)， fasting insulin， liver function (ALT， AST) were examined. HOMA-IR was calculated. Hepatic histological changes were observed. The content of TG， inflammatory factor (TNF-α， IL-8) and protein expressions of CD44， NF-κB p65， p-NF-κB p65 in hepatic tissues were determined. The ratio of p-NF-κB p65 to NF-κB p65 (p-p65/p65) was calculated. The result showed that compared with the model group， both PC treatment groups showed reduction in hepatic steatosis， inflammatory cell infiltration and fibroplasia in portal area. HOMA-IR， ALT， AST， FBG， PG-2 h， TC， TG， LDL-C concentrations and hepatic TG content were also significantly decreased， with the reduction of TNF-α， IL-8 contents， CD44 expression and p-p65/p65 ratio in hepatic tissues (P<0.01). High-dose PC group had a better effect than low-dose group (P<0.01， P<0.05). In conclusion， PC is effective in treating hepatic injury， glucolipid metabolism disturbances and fibrosis in juvenal NAFLD mice. The mechanism may be related to inhibition of inflammation and down-regulation of the activation of hepatic NF-κB.
, 百拇医药
[Key words] NAFLD；Psoralea corylifolia；inflammation；NF-κB；juvenal mouse
非酒精性脂肪性肝病(nonalcoholic fatty liver disease，NAFLD)呈現全球化、低龄化流行趋势，是儿童就诊消化专科或肝病专科的首要病因[1-3]。肥胖与脂肪肝关系密切，我国儿童肥胖症的流行已是客观事实[4-5]，肥胖儿童NAFLD患病率高达68.2%[2-3]。起源于儿童期的NAFLD更是成人肝硬化、代谢综合征相关疾病的主要后备人群[6]。随着我国城市化进程、中产家庭崛起及“二胎”政策的全面开放，NAFLD迅速蔓延，已取代慢性病毒性肝炎，成为威胁我国儿童健康的重大问题。
然而，目前临床尚缺乏针对儿童NAFLD的有效治疗药物[6-7]。近年来，“核因子κB(nuclear factor κB，NF-κB)”相关炎症通路在NAFLD发病机制中的重要地位被不断证实[8-9]。中药补骨脂(Psoralea corylifolia L.，PC)是儿科的传统常用药，具有温脾补肾壮阳的药用特点。该药的现代药理学研究主要与成人疾病相关，除抗肿瘤和改善骨质疏松等功效外，其肝脏保护及抗炎功效亦受到关注[10-11]。但是，PC对儿童脂肪肝的治疗作用及其机制研究未见报道，因此，本课题组通过建立幼龄小鼠脂肪肝动物模型，进一步探讨PC的抗脂肪肝作用及对肝组织NF-κB炎症通路的影响。, http://www.100md.com(周俪姗 鄢素琪 熊小丽 黄娟 张领领 汤建桥)
, 百拇医药
[关键词] 非酒精性脂肪性肝病；补骨脂；炎症；核因子κB；幼龄小鼠
[Abstract] To investigate the mechanism and effect of Psoralea corylifolia(PC) in the treatment of NAFLD in juvenal mice. The NAFLD model in juvenal mice was established by feeding high-fat diet. Then PC herbal granules (at low and high dose) were administered for 5 weeks. Blood glucose (FBG， PG-1 h/2 h)， blood lipid (TC， TG， HDL-C， LDL-C)， fasting insulin， liver function (ALT， AST) were examined. HOMA-IR was calculated. Hepatic histological changes were observed. The content of TG， inflammatory factor (TNF-α， IL-8) and protein expressions of CD44， NF-κB p65， p-NF-κB p65 in hepatic tissues were determined. The ratio of p-NF-κB p65 to NF-κB p65 (p-p65/p65) was calculated. The result showed that compared with the model group， both PC treatment groups showed reduction in hepatic steatosis， inflammatory cell infiltration and fibroplasia in portal area. HOMA-IR， ALT， AST， FBG， PG-2 h， TC， TG， LDL-C concentrations and hepatic TG content were also significantly decreased， with the reduction of TNF-α， IL-8 contents， CD44 expression and p-p65/p65 ratio in hepatic tissues (P<0.01). High-dose PC group had a better effect than low-dose group (P<0.01， P<0.05). In conclusion， PC is effective in treating hepatic injury， glucolipid metabolism disturbances and fibrosis in juvenal NAFLD mice. The mechanism may be related to inhibition of inflammation and down-regulation of the activation of hepatic NF-κB.
, 百拇医药
[Key words] NAFLD；Psoralea corylifolia；inflammation；NF-κB；juvenal mouse
非酒精性脂肪性肝病(nonalcoholic fatty liver disease，NAFLD)呈現全球化、低龄化流行趋势，是儿童就诊消化专科或肝病专科的首要病因[1-3]。肥胖与脂肪肝关系密切，我国儿童肥胖症的流行已是客观事实[4-5]，肥胖儿童NAFLD患病率高达68.2%[2-3]。起源于儿童期的NAFLD更是成人肝硬化、代谢综合征相关疾病的主要后备人群[6]。随着我国城市化进程、中产家庭崛起及“二胎”政策的全面开放，NAFLD迅速蔓延，已取代慢性病毒性肝炎，成为威胁我国儿童健康的重大问题。
然而，目前临床尚缺乏针对儿童NAFLD的有效治疗药物[6-7]。近年来，“核因子κB(nuclear factor κB，NF-κB)”相关炎症通路在NAFLD发病机制中的重要地位被不断证实[8-9]。中药补骨脂(Psoralea corylifolia L.，PC)是儿科的传统常用药，具有温脾补肾壮阳的药用特点。该药的现代药理学研究主要与成人疾病相关，除抗肿瘤和改善骨质疏松等功效外，其肝脏保护及抗炎功效亦受到关注[10-11]。但是，PC对儿童脂肪肝的治疗作用及其机制研究未见报道，因此，本课题组通过建立幼龄小鼠脂肪肝动物模型，进一步探讨PC的抗脂肪肝作用及对肝组织NF-κB炎症通路的影响。, http://www.100md.com(周俪姗 鄢素琪 熊小丽 黄娟 张领领 汤建桥)