目的:观察清血毒胶囊对银屑病模型小鼠治疗效果及组蛋白脱乙酰基酶1(HDAC1)、胶质瘤相关癌基因蛋白-1(Gli1)表达的影响。方法:60只BALB/c小鼠随机分为空白组、模型组、甲氨蝶呤组、清血毒胶囊低剂量组、清血毒胶囊中剂量组和清血毒胶囊...目的:观察清血毒胶囊对银屑病模型小鼠治疗效果及组蛋白脱乙酰基酶1(HDAC1)、胶质瘤相关癌基因蛋白-1(Gli1)表达的影响。方法:60只BALB/c小鼠随机分为空白组、模型组、甲氨蝶呤组、清血毒胶囊低剂量组、清血毒胶囊中剂量组和清血毒胶囊高剂量组,每组10只。采用5%咪喹莫特软膏制备寻常型银屑病小鼠模型,同时予治疗药物干预,各组均连续干预7 d。观察记录各组小鼠(第1天、第3天、第7天)皮损颜色、鳞屑程度、皮肤厚度并予银屑病皮损严重程度指数评分(Psoriasis Area and Severity Index,PASI);干预结束后,取皮损组织通过苏木精-伊红(HE)染色检测皮肤组织病理学变化并予Baker法评分;蛋白免疫印迹法检测皮损部HDAC1和Gli1的蛋白表达。结果:不同时间(第1天、第2天、第3天)之间小鼠PASI评分表达比较,差异有统计学意义(P<0.05),即存在时间效应。除空白组外,其余各组小鼠的PASI评分均逐渐上升。6组小鼠PASI评分总体比较,差异有统计学意义(P<0.05),即存在分组效应。时间因素和组别因素对PASI评分的影响存在交互效应(P<0.05)。干预7 d后,与空白组比较,模型组小鼠PASI评分、Baker法评分及HDAC1和Gli1的蛋白相对表达量均明显升高(P<0.05);与模型组比较,甲氨蝶呤组和清血毒胶囊中、高剂量组小鼠PASI评分、Baker法评分及HDAC1蛋白相对表达量均明显降低(P<0.05),清血毒胶囊低、中、高剂量组Gli1蛋白表达相对表达量均明显降低(P<0.05),且与药物浓度成负相关。结论:清血毒胶囊干预银屑病小鼠疗效肯定,其可能通过抑制HDAC1的表达,调控hedgehog(Hh)信号通路转录因子Gli1表达,抑制银屑病角质形成细胞异常增殖,发挥干预银屑病的作用。展开更多
Objective:This study investigated the potential mechanisms of Ganduqing Granule(GDQG)in improving the liver function in patients with chronic hepatitis B(CHB).Methods:Plasma samples from 30 healthy volunteers and 30 p...Objective:This study investigated the potential mechanisms of Ganduqing Granule(GDQG)in improving the liver function in patients with chronic hepatitis B(CHB).Methods:Plasma samples from 30 healthy volunteers and 30 patients with CHB before and after the treatment with GDQG were measured for the alterations in liver function and metabolites,using the method of ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry.Results:Patients with CHB developed severe liver dysfunction,which was associated with the higher plasma levels of 8 metabolites when compared with those of the normal control(P<0.05).Interestingly,after treatment with GDQG for 3 weeks,the 8 metabolites were significantly reduced(P<0.05).Among them,glycochenodeoxycholate-3-sulfate,glycochenodeoxycholic acid-3-glucuronide,taurochenodeoxycholic acid,and 7b-hydroxy-3-oxo-5b-cholanoic acid were associated with the metabolism of bile acids,while 3b,16a-dihydroxyandrostenone sulfate,lysophosphatidylcholine(C18:3),and lysophosphatidylethanolamine(C22:1)were related to the metabolism of lipids.2,6-Diamino-4-hydroxy-5-N-methylformamidopyrimidine was related to hepatic oxidative stress.Meanwhile,liver damage in patients was greatly reduced.Conclusion:Treatment with GDQG has improved liver function of patients with CHB through the possible mechanism of adjusting the metabolic disorders related to lipids,bile acids,and oxidative stress.展开更多
文摘目的:观察清血毒胶囊对银屑病模型小鼠治疗效果及组蛋白脱乙酰基酶1(HDAC1)、胶质瘤相关癌基因蛋白-1(Gli1)表达的影响。方法:60只BALB/c小鼠随机分为空白组、模型组、甲氨蝶呤组、清血毒胶囊低剂量组、清血毒胶囊中剂量组和清血毒胶囊高剂量组,每组10只。采用5%咪喹莫特软膏制备寻常型银屑病小鼠模型,同时予治疗药物干预,各组均连续干预7 d。观察记录各组小鼠(第1天、第3天、第7天)皮损颜色、鳞屑程度、皮肤厚度并予银屑病皮损严重程度指数评分(Psoriasis Area and Severity Index,PASI);干预结束后,取皮损组织通过苏木精-伊红(HE)染色检测皮肤组织病理学变化并予Baker法评分;蛋白免疫印迹法检测皮损部HDAC1和Gli1的蛋白表达。结果:不同时间(第1天、第2天、第3天)之间小鼠PASI评分表达比较,差异有统计学意义(P<0.05),即存在时间效应。除空白组外,其余各组小鼠的PASI评分均逐渐上升。6组小鼠PASI评分总体比较,差异有统计学意义(P<0.05),即存在分组效应。时间因素和组别因素对PASI评分的影响存在交互效应(P<0.05)。干预7 d后,与空白组比较,模型组小鼠PASI评分、Baker法评分及HDAC1和Gli1的蛋白相对表达量均明显升高(P<0.05);与模型组比较,甲氨蝶呤组和清血毒胶囊中、高剂量组小鼠PASI评分、Baker法评分及HDAC1蛋白相对表达量均明显降低(P<0.05),清血毒胶囊低、中、高剂量组Gli1蛋白表达相对表达量均明显降低(P<0.05),且与药物浓度成负相关。结论:清血毒胶囊干预银屑病小鼠疗效肯定,其可能通过抑制HDAC1的表达,调控hedgehog(Hh)信号通路转录因子Gli1表达,抑制银屑病角质形成细胞异常增殖,发挥干预银屑病的作用。
文摘Objective:This study investigated the potential mechanisms of Ganduqing Granule(GDQG)in improving the liver function in patients with chronic hepatitis B(CHB).Methods:Plasma samples from 30 healthy volunteers and 30 patients with CHB before and after the treatment with GDQG were measured for the alterations in liver function and metabolites,using the method of ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry.Results:Patients with CHB developed severe liver dysfunction,which was associated with the higher plasma levels of 8 metabolites when compared with those of the normal control(P<0.05).Interestingly,after treatment with GDQG for 3 weeks,the 8 metabolites were significantly reduced(P<0.05).Among them,glycochenodeoxycholate-3-sulfate,glycochenodeoxycholic acid-3-glucuronide,taurochenodeoxycholic acid,and 7b-hydroxy-3-oxo-5b-cholanoic acid were associated with the metabolism of bile acids,while 3b,16a-dihydroxyandrostenone sulfate,lysophosphatidylcholine(C18:3),and lysophosphatidylethanolamine(C22:1)were related to the metabolism of lipids.2,6-Diamino-4-hydroxy-5-N-methylformamidopyrimidine was related to hepatic oxidative stress.Meanwhile,liver damage in patients was greatly reduced.Conclusion:Treatment with GDQG has improved liver function of patients with CHB through the possible mechanism of adjusting the metabolic disorders related to lipids,bile acids,and oxidative stress.