Danggui Shaoyao powder improves hepatic lipid metabolism in atherosclerosis mice via PPARγ-LXRα-ABCA1 pathway regulation

Objective To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)pathway regulation.Methods Eight C57BL/6J male mice were selected as the control group,and 24 ApoE^(−/−)male mice were randomly divided into the atherosclerosis model(AS)group,atorvastatin calcium(AC)group,and DSP group(n=8 each group).To establish an AS model,ApoE^(−/−)mice were fed a high-fat diet for 16 weeks.Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining.Triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were determined in the livers using a single-reagent GPO-PAP method.Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver.Results After 16 weeks of a high-fat diet,ApoE−/−mice showed more Oil Red O staining in the aorta and liver compared to the CONT group.Compared to the AS group,the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees.Furthermore,DSP significantly reduced the hepatic lipid area in ApoE^(−/−)mice(P<.001)and decreased the levels of TG,TC,and LDL-C in liver(P<.001,P=.027,P<.001,respectively).DSP also significantly increased the levels of PPARγ,LXRα,ABCA1,and ABCG1 mRNA expression,as well as the PPARγ,LXRα,ABCA1,and ABCG1 protein expression in liver.Conclusion DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

探讨麻黄连翘赤小豆汤通过NLRP3细胞焦亡对特应性皮炎样小鼠模型的作用

目的:探讨麻黄连翘赤小豆汤(Mahuang Lianqiao Chixiaodou decoction,MLCD)通过NOD样受体蛋白3(NOD-like receptor protein 3,NLRP3)角质形成细胞焦亡途径干预特应性皮炎样(atopic dermatitis-like,AD样)小鼠皮肤屏障功能障碍与免疫炎症“内外串扰”的疗效及机制。方法:用2,4-二硝基氟苯诱导AD样模型小鼠,分别用MLCD或糠酸莫米松凝胶(mometasone furoate,MF,阳性对照组)处理7天。采用马松染色法、甲苯胺蓝染色法检测皮肤组织的病理变化与肥大细胞浸润情况。采用智能皮肤分析仪、流式细胞术、荧光定量聚合酶链反应和免疫印迹法观察和评估AD样小鼠的皮肤屏障功能障碍、免疫炎症反应和皮肤细胞焦亡。结果:MLCD和MF均可不同程度地改善AD样小鼠的皮损状态,减少病理组织损伤和肥大细胞浸润。MLCD显著降低皮肤色素沉着和炎症状态(P=0.005,P=0.038),增加脾脏中CD4^(+)CD3^(+)T细胞的百分比(P=0.022),降低CD8^(+)CD3^(+)T细胞百分比(P=0.044),降低CD8^(+)CD3^(+)/CD3^(+)的比值(P=0.031),并增加CD4^(+)CD3^(+)/CD8^(+)CD3^(+)的比值(P=0.027)。MLCD还可显著降低角质形成细胞焦亡相关因子NLRP3、casp-1、白细胞介素(IL)-1β和IL-18得mRNA相对表达水平(P=0.027、P<0.001、P=0.012和P=0.039)以及NLRP3、casp-1、凋亡相关斑点蛋白和IL-1β的蛋白表达水平(P=0.002、P=0.006、P=0.004和P=0.035)。结论:MLCD通过干预NLRP3角质形成细胞焦亡介导的皮肤屏障功能障碍和免疫炎症的“内外串扰”机制,对AD样小鼠的治疗具有疗效。