Protective effect of bicyclol against bile duct ligation-induced hepatic fibrosis in rats

AIM: To evaluate the protective effect of bicyclol against bile duct ligation(BDL)-induced hepatic fibrosis in rats.METHODS: Sprague-Dawley male rats underwent BDL and sham-operated animals were used as healthy controls. The BDL rats were divided into two groups which received sterilized PBS or bicyclol(100 mg/kg per day) orally for two consecutive weeks. Serum, urine and bile were collected for biochemical determinations. Liver tissues were collected for histological analysis and a whole genome oligonucleotide microarray assay. Reverse transcription-polymerase chain reaction and Western blotting were used to verify the expression of liver fibrosis-related genes.RESULTS: Treatment with bicyclol significantly reduced liver fibrosis and bile duct proliferation after BDL. The levels of alanine aminotransferase(127.7 ± 72.3 vs 230.4 ± 69.6, P < 0.05) and aspartate amino-transferase(696.8 ± 232.6 vs 1032.6 ± 165.8, P < 0.05) were also decreased by treatment with bicyclol in comparison to PBS. The expression changes of 45 fibrogenic genes and several fibrogenesis-related pathways were reversed by bicyclol in the microarray assay. Bicyclol significantly reduced liver m RNA and/or protein expression levels of collagen 1a1, matrix metalloproteinase 2, tumor necrosis factor, tissue inhibitors of metalloproteinases 2, transforming growth factor-b1 and α-smooth muscle actin.CONCLUSION: Bicyclol significantly attenuates BDLinduced liver fibrosis by reversing fibrogenic gene expression. These findings suggest that bicyclol might be an effective anti-fibrotic drug for the treatment of cholestatic liver disease.

Toxicity of novel anti-hepatitis drug bicyclol: A preclinical study

AIM: To study the toxicity of bicyclol to animals. METHODS: Acute toxicity test was performed in Kunming strain mice that were orally given bicyclol at the doses of 3 and 5 g/kg body weight, respectively. Wistar rats were orally administered bicyclol at a dose of 5 g/kg body weight. Death and clinical symptoms of animals were recorded within 7 d. Sub-acute toxicity test was carried out in rats that were treated with various doses of bicyclol (150, 300, 600 mg/kg) once daily for 14 d. Animal behaviors, blood biochemical markers, blood and urine pictures were examined. Chronic toxicity test was conducted in 80 Wistar rats of both sexes. The animals were orally administered with various doses of bicyclol [150, 300, 600 mg/kg, 100-400 folds corresponding to the proposed therapeutic dose (1.5 mg/(kg·d)) of bicyclol for patients] once daily for 6 mo except for Sunday. The control group was given the same volume of 0.2% sodium carboxyl methylcellulose (Na-CMC). Twenty-one beagle dogs received bicyclol (25, 75, 225 mg/kg, 16.6, 50, 150 folds corresponding to the proposed therapeutic dose of bicyclol for patients) once a day for 6 mo except for Sunday. The body weight, food intake, urine and feces, blood picture, blood biochemical markers, and pathological examination of main organs were determined. Mutagenicity and teratogenicity were determined. Mutagenicity assay included Ames's test, chromosome aberration test in CHL cells and micronucleus test in mice. For the teratogenicity assay, pregnant Wistar rats weighing 200-250 g were treated with 0.2,1.0 g/kg bicyclol once daily from the 7th d of gestation for 10 d. RESULTS: The oral LD50 of bicyclol was over 5 g/kg in mice and rats. No noticeable alterations in subacute and chronic toxicity of rats and dogs were demonstrated. No mutagenicity and teratogenicity of bicyclol were found. CONCLUSION: Bicyclol has no detectable chronic toxicity as well as mutagenicity and teratogenicity in animals.

Enantioseparation of Racemic Anti-hepatitis New Drug Bicyclol with Crystallization

The enantioseparation of anti-hepatitis new drug （±）-bicyclol was performed by optically active alkaloid. The alcoholic acid, the hydrolysate of bicyclol was reacted with optically active alkaloid, such as brucine, strychnine, quinidine etc., the diastereoisomeric salts were obtained by fractional recrystallization, then separately decomposed and esterified to obtain the two enantiomers of bicyclol. The pharmacological study showed that the effect of （-）-bicyclol was more potent than racemic bicyclol two times and the potency of （＋）-bicyclol was incative.

Clinical effect of microecological preparation combined with bicyclol on non-alcoholic fatty liver and its effect on liver fibrosis, blood lipid levels, serum inflammatory factors and TGF-β1

Objective:To investigate the clinical effect of microecological preparation combined with bicyclol on nonalcoholic fatty liver (NAFLD) and its effect on liver fibrosis, serum inflammatory factors and transforming growth factorβ1 (TGF-β1).Methods:106 patients with NAFLD were randomly divided into control group (53 cases) and case group (53 cases). The control group was given routine liver protection and bicyclol, and the case group was given Bifidobacterium triple viable probiotics based on the treatment of the control group. The two groups were treated for 6 weeks. The clinical effect, liver fibrosis, serum inflammatory factors, TGF-β1 and other changes were observed in the two groups after treatment.Results:The total effective rate of the case group was significantly higher than that of the control group (96.22% vs 83.02%), (χ2=4.970,P=0.026). After treatment, the ALB and HDL levels of the two groups of patients were higher than before. ALT, AST, and TBIL, LN, HA, PCIII, CIV, TC, TG, LDL, IL-6, TNF-a, hs-CRP, TGF-β1 were lower, compared with before and after treatment;and the improvement of liver function, liver fibrosis, blood lipid levels, serum inflammatory factors, and TGF-β1 in the case group was better than that in the control group, and the differences were statistically significant (P <0.05). The incidence of adverse reactions in the case group was lower than that in the control group (5.66% vs 11.32%). The difference was not statistically significant (χ2=1.093,P=0.296).Conclusion: Microecological preparations combined with bicyclol in the treatment of NAFLD have exact clinical effects, can significantly improve liver function, regulate blood lipid levels, reduce inflammation and liver fibrosis, and have good safety, which deserves further clinical research and promotion.

Reducing the oxidative stress mediates the cardioprotection of bicyclol against ischemia-reperfusion injury in rats

Objective:To investigate the beneficial effect of bicyclol on rat hearts subjected to ischemia-reperfusion(IR) injuries and its possible mechanism.Methods:Male Sprague-Dawley rats were intragastrically administered with bicyclol(25,50 or 100 mg/(kg·d)) for 3 d.Myocardial IR was produced by occlusion of the coronary artery for 1 h and reperfusion for 3 h.Left ventricular hemodynamics was continuously monitored.At the end of reperfusion,myocardial infarct was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining,and serum lactate dehydrogenase(LDH) level and myocardial superoxide dismutase(SOD) activity were determined by spectrophotometry.Isolated ventricular myocytes from adult rats were exposed to 60 min anoxia and 30 min reoxygenation to simulate IR injuries.After reperfusion,cell viability was determined with trypan blue;reactive oxygen species(ROS) and mitochondrial membrane potential of the cardiomyocytes were measured with the fluorescent probe.The mitochondrial permeability transition pore(mPTP) opening induced by Ca2+(200 μmol/L) was measured with the absorbance at 520 nm in the isolated myocardial mitochondria.Results:Low dose of bicyclol(25 mg/(kg·d)) had no significant improving effect on all cardiac parameters,whereas pretreatment with high bicyclol markedly reduced the myocardial infarct and improved the left ventricular contractility in the myocardium exposed to IR(P<0.05).Medium dose of bicyclol(50 mg/(kg·d)) markedly improved the myocardial contractility,left ventricular myocyte viability,and SOD activity,as well decreased infarct size,serum LDH level,ROS production,and mitochondrial membrane potential in rat myocardium exposed to IR.The reduction of ventricular myocyte viability in IR group was inhibited by pretreatment with 50 and 100 mg/(kg·d) bicyclol(P<0.05 vs.IR),but not by 25 mg/(kg·d) bicyclol.The opening of mPTP evoked by Ca2+ was significantly inhibited by medium bicyclol.Conclusions:Bicyclol exerts cardioprotection against IR injury,at least,via reducing oxidative stress and its subsequent mPTP opening.

Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication

Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.

Genotoxicity and Embryotoxicity Study of Bicyclol Methyl Ether, Main Impurity in Bicyclol

Objective: To assess the genotoxicity and embryotoxicity of bicyclol methyl ether(BME), the main impurity in bicyclol. Methods: Five concentrations of BME(0.5, 5, 50, 500 and 5000 μg/plate) were used in the Ames test to detect gene mutation. In the chromosome aberration test, Chinese hamster lung cells were used to detect chromosomal aberration of BME(15, 30, 60, 120 μg/m L) with or without S9 mixture. Embryotoxicity test was also conducted to determine any embryotoxicity of BME(7.5, 22.5, 67.5 μg/L) using zebrafish embryos. Results: No significant differences were observed in the Ames test and the chromosome aberration test in the BME groups compared with the vehicle control group. The zebrafish embryos toxicity test also showed no embryo development toxicity of BME, including hatching rate, body length, pericardial area and yolk sac area. Conclusions: Bicyclol methyl ether has no genotoxicity in vitro and embryotoxicity in zebrafish embryos, and the impurity in bicyclol is qualified.

双环醇联合益生菌治疗非酒精性脂肪肝的效果及对脂代谢、肝功能的影响

目的观察双环醇联合益生菌治疗非酒精性脂肪肝(NAFLD)的效果及其对脂代谢、肝功能的影响。方法2019年6月至2022年6月我院收治NAFLD患者102例,随机分为观察组和对照组,各51例,对照组给予双环醇片,观察组给予双环醇片和双歧杆菌三联活菌胶囊。检测治疗前后肝功能和脂代谢指标;比较两组临床疗效和安全性。结果观察组和对照组治疗总有效率分别为90.2%(46/51)、74.5%(38/51)(P<0.05);治疗后,两组血清AST分别为(49.2±11.5)U/L、(65.3±11.8)U/L,ALT分别为(50.8±13.2)U/L、(68.2±12.7)U/L,谷氨酰转肽酶(GGT)分别为(48.5±9.8)U/L、(61.2±10.3)U/L,差异有统计学意义(P<0.05);治疗后,两组血清甘油三酯(TG)分别为(1.8±0.4)mmol/L、(2.3±0.5)mmol/L,总胆固醇(TC)分别为(4.3±0.6)mmol/L、(5.1±0.8)mmol/L,低密度脂蛋白胆固醇(LDL-C)分别为(2.6±0.5)mmol/L、(3.5±0.7)mmol/L,差异有统计学意义(P<0.05)。两组高密度脂蛋白胆固醇(HDL-C)分别为(1.6±0.4)mmol/L、(1.3±0.4)mmol/L,差异有统计学意义(P<0.05)。治疗后,观察组肠球菌、大肠杆菌水平分别为(4.9±1.2)lgCFU/g、(6.2±0.9)lgCFU/g,明显低于对照组的(6.6±1.0)lgCFU/g、(6.9±1.2)lgCFU/g(P<0.05),观察组双歧杆菌、乳酸菌水平分别为(7.5±1.1)lgCFU/g、(6.8±1.3)lgCFU/g,明显高于对照组的(6.7±1.1)lgCFU/g、(5.9±0.9)lgCFU/g(P<0.05)。治疗后观察组出现不良反应9例(17.6%),包括乏力3例(5.9%)、食欲不振4例(7.8%)、失眠2例(3.9%),对照组不良反应5例(9.80%),包括乏力1例(2.0%)、食欲不振2例(3.9%)、失眠2例(3.9%),两组比较无明显差异(P>0.05)。结论采用双环醇联合益生菌治疗NAFLD患者有利于缓解肠道菌群紊乱,调控血脂水平,改善患者的肝功能,安全性较好。

双环醇防治肝脏炎性损伤多学科专家共识

肝脏炎性损伤是许多慢性肝病的始动因素。肝脏炎性损伤可累及全身,反之,全身疾病也会导致肝损伤。肝病的诊治既要考虑肝脏病变本身,又需了解全身各系统疾病与肝脏炎性损伤之间相互影响及其病理生理发生机制。因此,针对肝损伤的诊治,常需多学科讨论,共同决策。肝病治疗的重要环节之一是保护和维持肝功能的稳定,其中如何进行抗炎护肝是制定治疗策略的重要考量因素之一。双环醇是由我国自主研发、用于治疗肝脏炎性损伤的一类化学药物,对各种原因所致的肝脏炎性损伤均具有较好的防治作用,已于“一带一路”沿线九国注册并上市。为此,我们组织了国内相关学科专家,根据肝病诊疗相关指南/共识/临床路径和循证医学证据,结合我国临床实践,总结双环醇在防治肝脏炎性损伤多学科临床应用方面的进展,旨在形成共识,提高双环醇临床使用的科学性和规范性,提升各学科对肝脏炎性损伤的防治水平。

双环醇介导N6-甲基腺苷甲基化修饰影响大鼠心肌纤维化的作用研究

目的探讨双环醇对心肌纤维化模型大鼠的治疗作用及其可能的作用机制。方法选择无特定病原体级雄性SD大鼠24只,随机分为假手术组、模型组、低剂量组及高剂量组,每组6只。除假手术组外,其他各组尾静脉注射异丙肾上腺素5 mg/(kg·d)建立大鼠心肌纤维化模型,低剂量组、高剂量组分别按照100、200 mg/(kg·d)双环醇进行灌胃治疗,连续给药14 d。采用苏木精-伊红染色分析心肌损伤程度,Masson染色检测心肌纤维化程度,Western blot法检测心肌胶原蛋白Ⅰ、胶原蛋白Ⅲ、α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、甲基转移酶样蛋白3(methyltransferase-like protein 3(METTL3))、α-酮戊二酸依赖性双加氧酶ALKB同源物5(α-ketoglutarate-dependent dioxygenase alkB homolog5,ALKBH5)及YTH家族蛋白1(YTH domain family protein 1,YTHDF1)表达。结果与假手术组比较,模型组心肌细胞坏死程度明显升高,心肌纤维化程度增高;与模型组比较,低剂量组、高剂量组心肌细胞破裂和坏死程度明显降低,心肌纤维化程度明显改善。与假手术组比较,模型组心肌组织胶原蛋白Ⅰ、胶原蛋白Ⅲ、α-SMA、METTL3及YTHDF1表达明显升高(P<0.05),模型组ALKBH5表达明显降低(0.58±0.02 vs 0.88±0.07,P<0.05)。与模型组比较,低剂量组、高剂量组心肌组织胶原蛋白Ⅰ、胶原蛋白Ⅲ、α-SMA、METTL3及YTHDF1表达明显降低,ALKBH5表达明显升高,差异有统计学意义(P<0.05)。结论双环醇可有效缓解异丙肾上腺素诱导的心肌纤维化大鼠心肌结构损伤和间质胶原纤维化沉积,其机制可能与m^(6)A甲基化修饰相关。

双环醇抗脓毒症诱导的小鼠暴发性肝炎作用及机制研究

目的:探讨双环醇(Bicyclol)对脓毒症所致暴发性肝炎(FH)的防治作用及潜在机制。方法:采用脂多糖(LPS)/D-半乳糖(D-Gal)建立小鼠FH模型,灌胃给予Bicyclol处理,观察小鼠24 h内生存率;化学显色法检测血清谷草转氨酶(AST)和谷丙转氨酶(ALT)活性、肝组织过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)和丙二醛(MDA)水平;HE和TUNEL染色评估肝脏病理学变化;ELISA法检测血清白细胞介素6(IL-6)、白细胞介素1β(IL-1β)和血清肿瘤坏死因子α(TNF-α)水平;Western blotting检测肝组织核转录因子kappa B抑制蛋白α(IκBα)、磷酸化IκBα(p-IκBα)、核转录因子kappa B(NF-κB)、核红细胞2相关因子2(Nrf2)、NAD(P)H:醌氧化还原酶1(NQO1)和血红素加氧酶1(HO1)蛋白表达。结果:Bicyclol预处理提高FH小鼠生存率,降低ALT和AST活性,减轻肝组织病变,降低Suzuki评分(P<0.05,P<0.01)。同时,降低TNF-α、IL-1β、IL-6和MDA水平,升高GSH水平以及CAT和SOD酶活力,下调p-IκBα和胞核NF-κB表达,增加IκBα、胞核Nrf2、NQO1和HO1表达(P<0.05,P<0.01)。此外,Bicyclol治疗处理也显著降低FH小鼠血清ALT和AST活性(P<0.05,P<0.01)。结论:Bicyclol对LPS/D-Gal所致的FH具有显著防治作用,其作用机制可能与抑制NF-κB信号介导的炎症反应以及激活Nrf2/NQO1/HO1信号通路缓解氧化应激有关。

双环醇防治肝脏炎性损伤多学科专家共识

肝脏炎性损伤是许多慢性肝病的始动因素。肝脏炎性损伤可累及全身,反之,全身疾病也会导致肝损伤。肝病的诊治既要考虑肝脏病变本身,又需了解全身各系统疾病与肝脏炎性损伤之间相互影响及其病理生理发生机制。因此,针对肝损伤的诊治,常需多学科讨论,共同决策。肝病治疗的重要环节之一是保护和维持肝功能的稳定,其中如何进行抗炎护肝是制定治疗策略的重要考量因素之一。双环醇是由我国自主研发、用于治疗肝脏炎性损伤的一类化学药物,对各种原因所致的肝脏炎性损伤均具有较好的防治作用,已于“一带一路”沿线九国注册并上市。为此,本学组组织了国内相关学科专家,根据肝病诊疗相关指南/共识/临床路径和循证医学证据,结合我国临床实践,总结双环醇在防治肝脏炎性损伤多学科临床应用方面的进展,旨在形成共识,提高双环醇临床使用的科学性和规范性,提升各学科对肝脏炎性损伤的防治水平。

水飞蓟宾胶囊与双环醇片对60岁以上抗结核患者药物性肝损伤预防效果

目的 观察60岁以上初治结核病患者预防性保肝对降低药物性肝损伤(DILI)价值,进一步比较双环醇片与水飞蓟宾胶囊的保肝效果。方法 选取青岛市胸科医院2018年2月~2023年10月收治的186例结核病患者,均行强化治疗,对照组不给予保肝药,A组给予水飞蓟宾胶囊,B组给予双环醇片。比较3组患者治疗2、4和8周后DILI发生率。并于治疗前及治疗2、4和8周后检测3组患者超氧化物歧化酶(SOD)、血清谷胱甘肽过氧化物酶(GSH-Px)水平变化。比较3组患者不良反应发生率。结果 治疗第2和4周时,DILI发生率A组为6.34%、11.11%,B组为1.58%、9.52%,均低于对照组的11.11%、23.8%,其中B组与对照组比较差异有统计学意义(χ^(2)=4.805、4.628,P<0.05)。治疗第8周时,A组、B组DILI发生率12.69%、14.28%,均低于对照组的28.57%,差异有统计学意义(χ^(2)=4.846、3.818,P<0.05)。治疗2、4和8周3个时点B组SOD水平(338.59±36.25)U/L、(342.68±25.62)U/L、(345.28±37.36)U/L高于A组(228.06±23.83)U/L、(239.98±19.58)U/L、(246.25±28.73)U/L和对照组(217.69±15.66)U/L、(205.92±29.64)U/L、(226.34±28.51)U/L,且A组高于对照组,差异有统计学意义(F=2.187、2.664、2.823,P<0.05)。治疗2和4周时B组的GSH-Px水平(88.78±9.47)U/ml、(94.56±10.09)U/ml,较A组(80.66±6.26)U/ml、(88.89±9.35)U/ml和对照组(82.23±8.44)U/ml、(86.65±7.39)U/ml高,差异有统计学意义(t=5.677、3.271、4.098、5.019,P<0.05)。除DILI外,3组不良反应发生率分别为9.52%、12.69%、11.11%,差异无统计学意义(P> 0.05)。结论 对于60岁以上初治结核患者,可考虑给予预防性保肝治疗。水飞蓟宾胶囊与双环醇片均可降低DILI发生率,相较而言双环醇片起效更快。

双环醇联合甘草酸二铵对乙肝患者肝功能及肝纤维化程度的影响

目的探讨双环醇联合甘草酸二铵对乙肝患者肝功能及肝纤维化程度的影响。方法使用随机数字表法将2020年9月至2023年9月赣州市南康区第一人民医院收治的82例乙肝患者分为对照组与观察组。对照组(41例)予以甘草酸二铵,观察组(41例)予以双环醇联合甘草酸二铵。比较两组的肝功能及肝纤维化水平。结果与治疗前相比,两组治疗6周后的谷草转氨酶(AST)、谷丙转氨酶(ALT)和总胆红素(TBIL)的水平均明显下降(P<0.05)。观察组治疗后的粘连蛋白(LN)、透明质酸(HA)和Ⅲ型前胶原(HPCⅢ)均较治疗前降低,且低于对照组(P<0.05)。观察组肝硬度值(LSM)低于对照组(P<0.05)。观察组肝纤维化程度较对照组更低(P<0.05)。结论对乙肝患者给予双环醇联合甘草酸二铵的保肝治疗,临床疗效确切,可改善患者肝功能,减轻肝纤维化程度。

白芍总苷联合双环醇治疗轻症自身免疫性肝炎临床观察

目的:探讨白芍总苷联合双环醇治疗轻症自身免疫性肝炎(autoimmnue hepatitis,AIH)的临床疗效及安全性。方法:选取2020年4月-2023年4月收治的56例轻症AIH患者,随机分为治疗组与对照组,每组患者28例。治疗组给予白芍总苷(0.6 g/次,3次/天)联合双环醇(50 mg/次,3次/天)口服治疗,对照组仅给予双环醇(50 mg/次,3次/天)口服治疗,测定两组患者治疗基线,治疗12、24周的肝脏炎症学指标、免疫学相关指标、肝纤维化指标并记录药物相关不良反应。结果:24周后治疗组、对照组总有效率分别为89.29%、60.71%,差异具有统计学意义(P=0.037);两组患者ALT、AST、CD4^(+)T(%)、CD8^(+)T(%)、总球蛋白、IgG水平差异具有统计学意义(P<0.001),而ALP及肝硬度值(liver stiffness measurement,LSM)差异无统计学意义(P=0.570,0.671)。与对照组相比,24周后治疗组患者具有更低的ALT、AST、CD8^(+)T(%)、总球蛋白、IgG水平及更高的CD4^(+)T水平(P<0.001)。与基线相比,24周后两组患者LSM值均下降。两组患者不良反应发生率差异无明显统计学意义(P=1.0)。结论:白芍总苷联合双环醇治疗轻症AIH可以更好地改善肝脏炎症水平、调节机体免疫状态、控制肝纤维化进展且不增加药物不良反应发生率。

富马酸丙酚替诺福韦联合双环醇治疗慢性乙型肝炎合并脂肪肝的疗效

目的探究富马酸丙酚替诺福韦(TAF)联合双环醇治疗慢性乙型肝炎合并脂肪肝的效果。方法选择赣州市南康区第一人民医院2020年4月至2022年8月期间收治的88例慢性乙型肝炎合并脂肪肝患者为研究对象,按照随机数字表法分为对照组和观察组,每组44例。对照组给予TAF治疗,观察组给予TAF联合双环醇片治疗。治疗48周后比较两组治疗效果和相关指标的变化。结果治疗后,两组的血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性均较治疗前下降;观察组的肝脏脂肪控制衰减指数(CAP)水平较治疗前下降,且观察组的ALT、AST活性和CAP水平均较对照组低,差异有统计学意义(P<0.05);观察组血清乙型肝炎病毒DNA(HBV-DNA)、乙肝e抗原(HBeAg)水平和肝脏硬度值(LSM)均低于对照组,差异有统计学意义(P<0.05)。观察组的不良反应发生率为4.5%,低于对照组的27.3%(P<0.05)。结论采用富马酸丙酚替诺福韦联合双环醇对慢性乙型肝炎合并脂肪肝患者实施治疗,能改善患者肝功能和肝脏脂肪变程度,抑制病毒水平,安全性高。

双环醇联合还原型谷胱甘肽治疗抗结核药物所致药物性肝损伤患者的临床效果

目的 探讨双环醇联合还原型谷胱甘肽治疗抗结核药物所致药物性肝损伤(DILI)患者的临床效果。方法选取2021年1月至2022年12月我院收治的100例抗结核药物所致DILI患者,随机分为对照组和研究组各50例。对照组予以还原型谷胱甘肽治疗,研究组予以双环醇联合还原型谷胱甘肽治疗,均连续治疗3周。比较两组的临床疗效、肝功能指标[谷草转氨酶(AST)、丙氨酸转氨酶(ALT)、总胆红素(TBIL)、 γ-谷氨酰转肽酶(GGT)]及不良反应。结果 研究组治疗总有效率为96.00%,高于对照组的80.00%(P <0.05)。治疗后,研究组AST、 ALT、 TBIL、 GGT水平均低于对照组(P <0.05)。治疗期间,研究组不良反应发生率为10.00%,与对照组的6.00%比较无统计学差异(P>0.05)。结论 双环醇联合还原型谷胱甘肽治疗抗结核药物所致DILI患者,可明显提升临床疗效,改善患者肝功能,且安全可靠,值得临床推广应用。

双环醇对扑热息痛引起小鼠肝脏能量代谢和线粒体功能障碍的影响

目的 研究双环醇对扑热息痛 (对乙酰氨基酚 )引起小鼠肝能量代谢紊乱和线粒体功能障碍的保护作用。方法 小鼠ip扑热息痛 12 0mg·kg- 1 引起急性肝损伤 ,观察血清谷丙转氨酶 (ALT)和谷草转氨酶 (AST)水平、肝活体磷谱、肝线粒体膜流动性及线粒体ATPase活性的改变。结果 双环醇可显著抑制扑热息痛中毒小鼠PME ATP及PME PDE的升高。双环醇 (2 0 0mg·kg- 1 )可显著降低扑热息痛导致的线粒体膜流动性下降 ,并对线粒体ATPase活性降低有显著保护作用。结论 双环醇可保护扑热息痛导致的急性肝损伤 ,使肝脏能量代谢和磷脂代谢趋于正常 。

双环醇对刀豆蛋白A引起肝损伤小鼠肝脏基因表达谱的影响

本实验研究双环醇对刀豆蛋白A(concanavalin A,Con A)静脉注射引起免疫性肝损伤小鼠肝脏基因表达谱变化的影响,探讨双环醇肝保护作用的分子机制。小鼠于注射Con A26.5 mg.kg-1前24、8及1 h分别口服双环醇250 mg.kg-1。测定血清丙氨酸转氨酶(alanine aminotransferase,ALT)及天冬氨酸转氨酶(aspartateaminotransferase,AST)水平,提取小鼠肝脏总RNA,经反转录用Cy3-dUTP和Cy5-dUTP分别标记制备cDNA探针。将cDNA探针与BiostarM-40S小鼠基因表达谱芯片进行杂交,经ScanArray 4000扫描仪扫描芯片并用GenePix Pro 3.0软件进行分析。双环醇可显著抑制刀豆蛋白A引起的血清ALT和AST升高。与刀豆蛋白A对照组相比,双环醇给药组有287条基因发生差异表达,占芯片基因总数的7.00%。其中166条基因表达量明显下调,121条基因表达量明显上调。表达变化的基因主要涉及代谢与细胞色素P450、应激与炎症凋亡、细胞周期调控、信号传导以及再生等相关功能。双环醇对刀豆蛋白A引起小鼠肝损伤肝脏基因表达谱变化具有一定的影响,此结果对今后深入研究双环醇的肝脏保护作用特点和临床应用具有重要意义。

双环醇对大鼠肾脏缺血-再灌注损伤的保护作用

目的 观察双环醇对缺血 再灌注诱发肾损伤的保护作用。方法 在大鼠肾动脉缺血 再灌注模型上观察双环醇对肾缺血 再灌注引起的血清丙二醛 (MDA)、尿素氮 (BUN) ,肾脏还原型谷胱甘肽 (GSH)、谷胱甘肽巯基转移酶 (GST)及肾线粒体膜流动性改变的影响。结果 双环醇ig 5 0及 2 0 0mg·kg- 1 可剂量依赖性保护缺血 再灌注引起的血清MDA及BUN升高、肾GSH含量降低 ,同时可诱导GST活性 ,缓解由于缺血 再灌注损伤引起的线粒体膜流动性降低。结论 双环醇对肾缺血