Objective:To investigate the effect of curcumol on NOD-like receptor thermoprotein domain 3(NLRP3)inflammasomes,and analyze the mechanism underlying curcumol against liver fibrosis.Methods:Thirty Kunming mice were div...Objective:To investigate the effect of curcumol on NOD-like receptor thermoprotein domain 3(NLRP3)inflammasomes,and analyze the mechanism underlying curcumol against liver fibrosis.Methods:Thirty Kunming mice were divided into a control group,a model group and a curcumol group according to a random number table,10 mice in each group.Mice were intraperitoneally injected with 40% carbon tetrachloride(CCl4:peanut oil,2:3 preparation)at 5 m L/kg for 6 weeks,twice a week,for developing a liver fibrosis model.The mice in the control group were given the same amount of peanut oil,twice a week for 6 weeks.The mice in the curcumol group were given curcumol(30 m L/kg)intragastrically,and the mice in the model and control groups were given the same amount of normal saline,once a day for 6 weeks.Changes in liver structure were observed by hematoxylin and eosin(HE)and Masson staining.Liver function,liver fiber indices,and the expression of interleukin(IL)-10 and tumor necrosis factor-α(TNF-α)levels were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay kit.Immunoblotting and reverse transcription-quantitative PCR(RT-qPCR)were performed to detect the expression of NLRP3 inflammasome-related molecules,TGF-β and collagen.Results:HE and Masson staining results showed that the hepatocytes of the model group were arranged irregularly with pseudo-lobular structure and a large amount of collagen deposition.The mice in the curcumol group had a significant decrease in liver function and liver fibers indices compared with the model group(P<0.05);RT-qPCR and Western blot results reveal that,in the curcumol group,the mRNA and protein expression levels of NLRP3,IL-1β,Caspase 1 and gasdermin D decreased significantly compared with the model group(P<0.05);immunohistochemical results showed that in the curcumol group,the protein expression levels of NLRP3 and IL-1β decreased significantly compared with the model group(P<0.05).Conclusion:A potential anti-liver fibrosis mechanism of curcumol may be associated with the inhibition of NLRP3 inflammasomes and decreasing the downstream inflammatory response.展开更多
目的评价富氢液对大鼠心搏骤停/心肺复苏大鼠脑损伤海马NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体表达的影响。方法清洁级雄性SD大鼠80只,体重280~350 g,8~10周龄...目的评价富氢液对大鼠心搏骤停/心肺复苏大鼠脑损伤海马NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体表达的影响。方法清洁级雄性SD大鼠80只,体重280~350 g,8~10周龄,采用随机数字表法分为3组:假手术组(Sham组,n=20)、心脏停搏心肺复苏组(I/R组,n=30)和富氢液组(H组,n=30)。采用经食管电刺激法建立心脏停搏心肺复苏模型;Sham组大鼠只进行气管插管及动静脉穿刺,于自主循环恢复(ROSC)即刻及6 h腹腔内注射富氢液5 ml/kg;其余2组腹腔内注射等容量的生理盐水。于ROSC后48 h行神经功能评分(NDS);H-E染色观察CA1区并计数锥体细胞;采用Western blot法检测海马NLRP3、半胱天冬酶-1前体(pro-caspase-1)和凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)的表达。结果与Sham组比较,I/R组和H组ROSC 48 h后神经功能评分降低(P<0.05),锥体细胞计数减少(P<0.05),海马NLRP3、pro caspase-1和ASC表达上调(P<0.05);与I/R组比较,H组神经功能评分升高(P<0.05),锥体细胞计数增多(P<0.05),海马NLRP3、pro caspase-1和ASC表达下调(P<0.05)。结论富氢液减轻心搏骤停/心肺复苏大鼠脑损伤的机制可能与抑制NLRP3炎症小体激活、减轻炎症反应有关。展开更多
基金Supported by the National Natural Science Foundation of China(No.81960751,81660705)Guangxi Young and Middle-aged Teachers’Research Ability Improvement Project(No.2020KY59009)+2 种基金Guangxi Zhuangyao Pharmaceutical Key Laboratory(No.GXZYZZ2019-1,GXZYZZ2020-07)Guangxi Natural Science Foundation Youth Project(No.2020GXNSFBA297094)Guangxi University of Traditional Chinese Medicine School-level Project Youth Fund(No.2020QN006)。
文摘Objective:To investigate the effect of curcumol on NOD-like receptor thermoprotein domain 3(NLRP3)inflammasomes,and analyze the mechanism underlying curcumol against liver fibrosis.Methods:Thirty Kunming mice were divided into a control group,a model group and a curcumol group according to a random number table,10 mice in each group.Mice were intraperitoneally injected with 40% carbon tetrachloride(CCl4:peanut oil,2:3 preparation)at 5 m L/kg for 6 weeks,twice a week,for developing a liver fibrosis model.The mice in the control group were given the same amount of peanut oil,twice a week for 6 weeks.The mice in the curcumol group were given curcumol(30 m L/kg)intragastrically,and the mice in the model and control groups were given the same amount of normal saline,once a day for 6 weeks.Changes in liver structure were observed by hematoxylin and eosin(HE)and Masson staining.Liver function,liver fiber indices,and the expression of interleukin(IL)-10 and tumor necrosis factor-α(TNF-α)levels were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay kit.Immunoblotting and reverse transcription-quantitative PCR(RT-qPCR)were performed to detect the expression of NLRP3 inflammasome-related molecules,TGF-β and collagen.Results:HE and Masson staining results showed that the hepatocytes of the model group were arranged irregularly with pseudo-lobular structure and a large amount of collagen deposition.The mice in the curcumol group had a significant decrease in liver function and liver fibers indices compared with the model group(P<0.05);RT-qPCR and Western blot results reveal that,in the curcumol group,the mRNA and protein expression levels of NLRP3,IL-1β,Caspase 1 and gasdermin D decreased significantly compared with the model group(P<0.05);immunohistochemical results showed that in the curcumol group,the protein expression levels of NLRP3 and IL-1β decreased significantly compared with the model group(P<0.05).Conclusion:A potential anti-liver fibrosis mechanism of curcumol may be associated with the inhibition of NLRP3 inflammasomes and decreasing the downstream inflammatory response.
