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目的:研究疏肝健脾方对非酒精性脂肪性肝炎(NASH)的干预作用及其机制。方法:40只雄性C57/BL6小鼠随机分为随机分为胆碱蛋氨酸充足(MCS)组、胆碱蛋氨酸缺乏(MCD)组、胆碱蛋氨酸缺含(MCD)组、健脾疏肝方(JP)组及复方蛋氨酸胆碱片(CMCB)组,每组10只。除MCS组外,采用MCD饮食诱导小鼠NASH模型。造模同时JP组小鼠予以疏肝健脾方中药煎剂灌胃给药2周(21.63g/kg),CMCB组予以CMCB溶液灌胃2周(274.6mg/kg),每日1次;MCS组和MCD组予以二甲基亚砜(DMSO)灌胃2周(1m L/10g),每日1次。2周后,处死动物,取血清和肝组织。观察肝组织病理学变化,检测肝功能、炎性因子、脂代谢、氧化应激及脂质过氧化相关指标,并进行相关因子的蛋白水平检测。结果:与MCD组比较,JP组肝组织病理变化明显改善,NAS病理评分显著降低(P=0.000);血清丙氨酸氨基转酶(ALT)活性、肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)水平显著下降(P=0.000),肝组织甘油三酯(TG)(P=0.000)、丙二醛(MDA)水平(P=0.006)及核因子κB(NF-κB)表达(P=0.047)显著下降,肝组织肝性脂肪酸结合蛋白(L-FABP)表达显著升高(P=0.016)。CMCB组在降低血清ALT、TNF-α水平方面优于JP组(P<0.05),但在降低肝组织TG、血清TC及LDL方面效果不如JP组(P<0.05,P<0.01)。结论:健脾疏肝方通过多条途径对NASH起到正向干预作用。健脾疏肝方可抑制NF-κB的表达,抑制炎性因子的生成,调控炎性信号传导通路;并可通过增加L-FABP表达调控肝组织脂质转运及代谢,减少氧化应激反应,抑制脂质过氧化。
Objective: To investigate the effect of Shugan Jianpi Fang on non-alcoholic steatohepatitis (NASH) and its mechanism. Methods: Forty male C57 / BL6 mice were randomly divided into three groups: MCS group, MCD group, MCD group, Jianpi Shugan Fang JP) group and compound methionine choline (CMCB) group, 10 in each group. In addition to the MCS group, the mouse NASH model was induced using the MCD diet. At the same time, the mice in JP group were treated with Shuganjianpi decoction by intragastric administration for 2 weeks (21.63g / kg), CMCB group by intragastric administration of CMCB solution for 2 weeks (274.6mg / kg) MCS group and MCD group were given dimethyl sulfoxide (DMSO) for 2 weeks (1m L / 10g), once daily. After 2 weeks, animals were sacrificed and serum and liver tissues were taken. The pathological changes of liver tissue were observed, liver function, inflammatory factors, lipid metabolism, oxidative stress and lipid peroxidation were detected, and protein levels of related factors were detected. Results: Compared with MCD group, pathological changes of liver tissue in JP group were significantly improved and NAS pathology score was significantly decreased (P = 0.000). Serum alanine aminotransferase (ALT) activity, tumor necrosis factor alpha (TNF-α) and leukocyte (P = 0.000), TG (P = 0.000), MDA (P = 0.006), and nuclear factor kappa B (NF- κB expression (P = 0.047), the expression of hepatic fatty acid binding protein (L-FABP) in liver tissue was significantly increased (P = 0.016). CMCB group was superior to JP group (P <0.05) in reducing serum ALT and TNF-α levels, but not as effective as JP group (P <0.05, P <0.01) in reducing TG, serum TC and LDL in liver tissue. Conclusion: Jianpi Shugan Fang has positive effects on NASH through multiple pathways. Jianpi Shugan decoction can inhibit the expression of NF-κB, inhibit the production of inflammatory cytokines and regulate the inflammatory signal transduction pathway. It can also regulate lipid transport and metabolism of liver tissue and reduce oxidative stress by increasing L-FABP expression, Inhibits lipid peroxidation.