目的:研究茵陈醇提物对游离脂肪酸刺激HepG2细胞所致肝脂毒性的抑制作用及机制。方法:制备大鼠的正常血清和药物血清,在经毒性试验确定无药物毒性的前提下,分设正常组、模型组和茵陈醇提物组(10%,1%,0.1%3个剂量),以相应浓度的正常血清...目的:研究茵陈醇提物对游离脂肪酸刺激HepG2细胞所致肝脂毒性的抑制作用及机制。方法:制备大鼠的正常血清和药物血清,在经毒性试验确定无药物毒性的前提下,分设正常组、模型组和茵陈醇提物组(10%,1%,0.1%3个剂量),以相应浓度的正常血清和药物血清培养HepG2细胞,同时添加长链游离脂肪酸(FFA)刺激HepG2细胞24 h。观察:①细胞上清肿瘤坏死因子(TNF-α)含量(ELISA法);②细胞内甘油三酯(TG)含量、细胞脂肪油红O染色;③细胞内磷酸化κB抑制蛋白(P-IκB)、组织蛋白酶B(ctsb)、凋亡抑制基因相关X蛋白(Bax)蛋白表达(W estern B lotting法);④细胞TNF-,αctsb和Bax基因表达(real-tim e PCR);⑤细胞内ctsb的表达和分布(免疫荧光法)。结果:模型组细胞内TG及上清TNF-α含量显著升高,分别达(590±186)mg.g-1,(77±11)pg.mg-1,细胞内ctsb,P-IκB的蛋白表达以及ctsb,TNF-α的mRNA表达显著增强;而10%茵陈醇提物组细胞内TG和上清TNF-α含量较模型组显著降低,仅为(335±54)mg.g-1,(55±7)pg.mg-1,且显著抑制细胞内ctsb,P-IκB的蛋白表达以及ctsb,TNF-α的mRNA表达。结论:茵陈醇提物对FFA诱导的HepG2细胞脂肪变性,TNF-α分泌有显著的抑制作用,其作用与抑制ctsb等基因和蛋白表达有关。展开更多
Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the ob...Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.展开更多
The pathogenesis of liver damage associated with chronic hepatitis C virus (HCV) infection is thought to be largely immunomediated. However, some frequent histoo pathological features, such as steatosis, suggest a d...The pathogenesis of liver damage associated with chronic hepatitis C virus (HCV) infection is thought to be largely immunomediated. However, some frequent histoo pathological features, such as steatosis, suggest a direct cytopathic effect of HCV. The direct responsibility of HCV in the pathogenesis of steatosis is shown by: (1) the association with HCV genotype 3 infection, suggesting that some viral sequences are involved in the intracellular aco cumulation of lipids; (2) the correlation between severity of steatosis and HCV replication levels; (3) association between response to treatment and disappearance of steatosis. Experimental studies have shown that the nuo cleocapsid protein of HCV (core protein) is capable and sufficient to induce lipid accumulation in hepatocytes. Moreover, the observation that chronic hepatitis C pao tients have reduced serum levels of ApoB suggests an interference with the very-low density lipoprotein (VLDL) assembly, although other mechanisms are possible. In patients with sustained virological response induced by antiviral therapy, such levels are normalized. Other obo servations suggest that the pathogenesis of steatosis in chronic hepatitis C is not solely due to HCV. The origin of the mild steatosis observed in most patients may be metabolic, since its severity correlates with body mass index and insulin resistance. Most studies have shown a correlation between presence and/or severity of steatosis and fibrosis stage, but it is unclear whether this effect is direct or mediated by the associated insulin resistance, increased susceptibility to apoptosis, or by inflammao tory cytokines. Finally, steatosis negatively influences the rate of response to antiviral treatment, as confirmed by large clinical trials. Management of steatosis in chronic hepatitis C requires knowledge of its pathogenesis and may involve both life-style changes and pharmacological interventions, although the latter remain largely experio mental.展开更多
AIM: To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-α), Toll-like receptor 4 (TLR4), and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats. METHODS: Male F3...AIM: To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-α), Toll-like receptor 4 (TLR4), and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats. METHODS: Male F344 rats were fed a cholinedeficient L-amino-acid-defined (CDAA) diet. The rats were killed after 4 or 8 wk of the diet, and their livers were removed for immunohistochemical investigation and RNA extraction. The liver specimens were immunostained for TNF-α, TLR4, and CD14. The gene expressions of TNF-α, TLR4, and CD14 were determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Kupffer cells were isolated from the liver by Percoll gradient centrifugation, and were then cultured to measure TNF-α production. RESULTS: The serum and liver levels of TNF-~ in the CDAA-fed rats increased significantly as compared with the control group, as did the immunohistochemical values and gene expressions of TNF-α, TLR4, and CD14 with the progression of steatohepatitis. TNF-α production from the isolated Kupffer cells of the CDAAfed rats was elevated by lipopolysaccharide stimulation. CONCLUSION: The expressions of TNF-α, TLR4, and CD14 increased in the NASH model, suggesting that展开更多
Guillain-Barrésyndrome(GBS)is often triggered by a preceding bacterial or viral infection.Occasionally,it has been observed in association with acute hepatitis A,B and C,and three cases have been previously descr...Guillain-Barrésyndrome(GBS)is often triggered by a preceding bacterial or viral infection.Occasionally,it has been observed in association with acute hepatitis A,B and C,and three cases have been previously described in India in which GBS was associated with acute hepatitis E.A molecular mimicry mechanism is supposed to be involved in the pathogenesis of GBS triggered by infectious agents,although the nature of the shared epitopes has not been characterized in most instances,including that in the case of hepatotropic viruses.We report a case of GBS following acute hepatitis E in a European individual.The presence of antiganglioside GM2 antibodies in this patient suggested molecular mimicry involving ganglioside GM2 in the pathogenesis of GBS associated with hepatitis E.展开更多
Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a cha...Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be "lethal", which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings: M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picomaviruses.展开更多
OBJECTIVE: To investigate the potential chronic liver toxicity of oral administration of ethanol extract of Huangqin(Radix Scutellariae Baicalensis)(SBE) in Wistar rats.METHODS: SBE was administered to rats by gavage ...OBJECTIVE: To investigate the potential chronic liver toxicity of oral administration of ethanol extract of Huangqin(Radix Scutellariae Baicalensis)(SBE) in Wistar rats.METHODS: SBE was administered to rats by gavage for 26 weeks, at doses of 300, 1250, or 2500 mg·kg-1·d-1 respectively. The rats were euthanized at the end of 13 and 26 weeks daily oral dosing and following 4 weeks of recovery time. The changes of hematology, urinary, blood biochemistry and histomorphology were examined at each time point and focus on liver function and histological changes.RESULTS: When SBE at a dose of up to 2500 mgkg-1 d-1 was fed to male and female rats for 2··6 weeks, the liver tissue showed some inflammatory change that predominated by leukocyte infiltrationbut returned to normal after withdrawal. In addition, high-dose SBE treatment of 26 weeks in rats,glucose, electrolyte and lipid levels also have some changes. In addition, there are no other functional or organic lesions related to SBE treatment.CONCLUSIONS: Long-term and high-dose SBE may cause liver damage, however, the structural damage of the liver can be restored after the ethanol extract stopping. SBE will be well-tolerated for long-term use as a drug or health food, but in order to ensure drug safety, liver function, and serum glucose, electrolyte and lipid levels should be monitored when using SBE long term.展开更多
文摘目的:研究茵陈醇提物对游离脂肪酸刺激HepG2细胞所致肝脂毒性的抑制作用及机制。方法:制备大鼠的正常血清和药物血清,在经毒性试验确定无药物毒性的前提下,分设正常组、模型组和茵陈醇提物组(10%,1%,0.1%3个剂量),以相应浓度的正常血清和药物血清培养HepG2细胞,同时添加长链游离脂肪酸(FFA)刺激HepG2细胞24 h。观察:①细胞上清肿瘤坏死因子(TNF-α)含量(ELISA法);②细胞内甘油三酯(TG)含量、细胞脂肪油红O染色;③细胞内磷酸化κB抑制蛋白(P-IκB)、组织蛋白酶B(ctsb)、凋亡抑制基因相关X蛋白(Bax)蛋白表达(W estern B lotting法);④细胞TNF-,αctsb和Bax基因表达(real-tim e PCR);⑤细胞内ctsb的表达和分布(免疫荧光法)。结果:模型组细胞内TG及上清TNF-α含量显著升高,分别达(590±186)mg.g-1,(77±11)pg.mg-1,细胞内ctsb,P-IκB的蛋白表达以及ctsb,TNF-α的mRNA表达显著增强;而10%茵陈醇提物组细胞内TG和上清TNF-α含量较模型组显著降低,仅为(335±54)mg.g-1,(55±7)pg.mg-1,且显著抑制细胞内ctsb,P-IκB的蛋白表达以及ctsb,TNF-α的mRNA表达。结论:茵陈醇提物对FFA诱导的HepG2细胞脂肪变性,TNF-α分泌有显著的抑制作用,其作用与抑制ctsb等基因和蛋白表达有关。
文摘Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.
基金Supported by the Swiss National Science Foundation grant, No. 3200B0-103727/1
文摘The pathogenesis of liver damage associated with chronic hepatitis C virus (HCV) infection is thought to be largely immunomediated. However, some frequent histoo pathological features, such as steatosis, suggest a direct cytopathic effect of HCV. The direct responsibility of HCV in the pathogenesis of steatosis is shown by: (1) the association with HCV genotype 3 infection, suggesting that some viral sequences are involved in the intracellular aco cumulation of lipids; (2) the correlation between severity of steatosis and HCV replication levels; (3) association between response to treatment and disappearance of steatosis. Experimental studies have shown that the nuo cleocapsid protein of HCV (core protein) is capable and sufficient to induce lipid accumulation in hepatocytes. Moreover, the observation that chronic hepatitis C pao tients have reduced serum levels of ApoB suggests an interference with the very-low density lipoprotein (VLDL) assembly, although other mechanisms are possible. In patients with sustained virological response induced by antiviral therapy, such levels are normalized. Other obo servations suggest that the pathogenesis of steatosis in chronic hepatitis C is not solely due to HCV. The origin of the mild steatosis observed in most patients may be metabolic, since its severity correlates with body mass index and insulin resistance. Most studies have shown a correlation between presence and/or severity of steatosis and fibrosis stage, but it is unclear whether this effect is direct or mediated by the associated insulin resistance, increased susceptibility to apoptosis, or by inflammao tory cytokines. Finally, steatosis negatively influences the rate of response to antiviral treatment, as confirmed by large clinical trials. Management of steatosis in chronic hepatitis C requires knowledge of its pathogenesis and may involve both life-style changes and pharmacological interventions, although the latter remain largely experio mental.
基金Supported by Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology of Japan,No.19590784
文摘AIM: To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-α), Toll-like receptor 4 (TLR4), and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats. METHODS: Male F344 rats were fed a cholinedeficient L-amino-acid-defined (CDAA) diet. The rats were killed after 4 or 8 wk of the diet, and their livers were removed for immunohistochemical investigation and RNA extraction. The liver specimens were immunostained for TNF-α, TLR4, and CD14. The gene expressions of TNF-α, TLR4, and CD14 were determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Kupffer cells were isolated from the liver by Percoll gradient centrifugation, and were then cultured to measure TNF-α production. RESULTS: The serum and liver levels of TNF-~ in the CDAA-fed rats increased significantly as compared with the control group, as did the immunohistochemical values and gene expressions of TNF-α, TLR4, and CD14 with the progression of steatohepatitis. TNF-α production from the isolated Kupffer cells of the CDAAfed rats was elevated by lipopolysaccharide stimulation. CONCLUSION: The expressions of TNF-α, TLR4, and CD14 increased in the NASH model, suggesting that
文摘Guillain-Barrésyndrome(GBS)is often triggered by a preceding bacterial or viral infection.Occasionally,it has been observed in association with acute hepatitis A,B and C,and three cases have been previously described in India in which GBS was associated with acute hepatitis E.A molecular mimicry mechanism is supposed to be involved in the pathogenesis of GBS triggered by infectious agents,although the nature of the shared epitopes has not been characterized in most instances,including that in the case of hepatotropic viruses.We report a case of GBS following acute hepatitis E in a European individual.The presence of antiganglioside GM2 antibodies in this patient suggested molecular mimicry involving ganglioside GM2 in the pathogenesis of GBS associated with hepatitis E.
文摘Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be "lethal", which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings: M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picomaviruses.
基金Supported by Major National Science and Technology Projects of China(No.2015ZX09501004No.2014 ZX09304307001+1 种基金No.2014ZX09201022-004)Beijing Science and Technology Projects(No.Z161100004916025,No.Z151100000115012)
文摘OBJECTIVE: To investigate the potential chronic liver toxicity of oral administration of ethanol extract of Huangqin(Radix Scutellariae Baicalensis)(SBE) in Wistar rats.METHODS: SBE was administered to rats by gavage for 26 weeks, at doses of 300, 1250, or 2500 mg·kg-1·d-1 respectively. The rats were euthanized at the end of 13 and 26 weeks daily oral dosing and following 4 weeks of recovery time. The changes of hematology, urinary, blood biochemistry and histomorphology were examined at each time point and focus on liver function and histological changes.RESULTS: When SBE at a dose of up to 2500 mgkg-1 d-1 was fed to male and female rats for 2··6 weeks, the liver tissue showed some inflammatory change that predominated by leukocyte infiltrationbut returned to normal after withdrawal. In addition, high-dose SBE treatment of 26 weeks in rats,glucose, electrolyte and lipid levels also have some changes. In addition, there are no other functional or organic lesions related to SBE treatment.CONCLUSIONS: Long-term and high-dose SBE may cause liver damage, however, the structural damage of the liver can be restored after the ethanol extract stopping. SBE will be well-tolerated for long-term use as a drug or health food, but in order to ensure drug safety, liver function, and serum glucose, electrolyte and lipid levels should be monitored when using SBE long term.