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.

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.

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 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.

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。

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。

益生菌联合双环醇治疗非酒精性脂肪性肝病临床观察

目的探讨益生菌联合双环醇治疗非酒精性脂肪性肝病(NAFLD)的临床疗效。方法选取医院2020年4月至2021年9月收治的NAFLD患者92例,按随机数字表法分为对照组和观察组,各46例。对照组患者口服双环醇片,观察组患者在此基础上口服枯草杆菌二联活菌肠溶胶囊,均连续治疗3个月。结果观察组总有效率为95.65%,显著高于对照组的84.78%(P<0.05)。治疗后,两组患者的肝酶指标(丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、谷氨酰转移酶)水平均显著降低,且观察组均显著更低(P<0.05);血脂代谢指标(三酰甘油、总胆固醇)水平及体质量指数均显著降低,且观察组均显著更低(P<0.05);白细胞介素6和脂多糖水平均显著降低,且观察组均显著更低(P<0.05)。治疗后,观察组患者脂肪肝完全消退率为21.74%,显著高于对照组的13.04%(P<0.05)。结论益生菌联合双环醇治疗NAFLD的短期疗效良好,可有效改善患者的肝功能及血脂代谢水平,降低血清IL-6和LPS水平,且安全性良好。

还原型谷胱甘肽联合双环醇对抗结核药物导致肝损伤患者肝功能和氧化应激反应的影响

目的:探讨还原型谷胱甘肽联合双环醇对抗结核药物导致肝损伤患者肝功能和氧化应激反应的影响。方法:选择2019年1月至2021年5月于该院就诊的抗结核药物导致肝损伤的患者200例,依据随机数字表法分为对照组和治疗组,每组100例。对照组患者采用双环醇治疗,1次25 mg, 1日3次。治疗组患者在对照组的基础上将还原型谷胱甘肽1.8 g加入5%葡萄糖注射液250 mL中,静脉滴注,1日1次。两组患者均连续治疗4周。观察两组患者治疗前后的肝功能指标[血清丙氨酸转氨酶(ALT)、总胆红素(TBIL)和天冬氨酸转氨酶(AST)]、氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)]水平,比较疗效和不良反应发生情况。结果:治疗2、4周后,两组患者血清ALT、TBIL及AST水平,MDA、SOD和GSH-Px水平较治疗前显著改善,治疗组患者治疗后的改善效果较对照组更为明显,差异均有统计学意义(P<0.05)。观察组患者的总有效率为96.00%(96/100),明显高于对照组的76.00%(76/100),差异有统计学意义(P<0.05)。两组患者皮疹、头晕、胃肠道不适和失眠等不良反应发生率的差异无统计学意义(P>0.05)。结论:还原型谷胱甘肽联合双环醇用于抗结核药物导致肝损伤患者的临床疗效显著,能够有效改善肝功能指标,缓解氧化应激反应。

更昔洛韦联合双环醇治疗儿童EB病毒感染传染性单核细胞增多症的临床效果观察

目的观察更昔洛韦联合双环醇治疗儿童EB病毒感染传染性单核细胞增多症的临床效果。方法选取2017年6月至2021年12月我院收治的80例EB病毒感染传染性单核细胞增多症患儿,随机分为对照组和观察组各40例。对照组采用更昔洛韦治疗,观察组采用更昔洛韦联合双环醇治疗。比较两组患儿的治疗效果、相关症状缓解时间及不良反应发生情况。结果观察组治疗总有效率为90.0%,高于对照组的72.5%(P<0.05)。观察组的高热消退时间、淋巴结肿大消失时间、肝功能指标恢复正常时间、异型淋巴细胞<10%时间及肝脏肿大消失时间均短于对照组(P<0.05)。两组的不良反应发生率(12.5%vs.5.0%)比较差异无统计学意义(P>0.05)。结论更昔洛韦联合双环醇治疗儿童EB病毒感染传染性单核细胞增多症的临床效果显著,可有效改善患儿临床症状,且安全性较高,值得临床推广。

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

双环醇联合更昔洛韦治疗婴儿巨细胞病毒感染性肝炎的临床效果

目的评价双环醇联合更昔洛韦治疗婴儿巨细胞病毒感染性肝炎的治疗效果。方法将70例巨细胞病毒感染性肝炎患儿随机分为治疗组35例与对照组35例。两组均给予更昔洛韦5 mg/kg·次,2次/d静脉输注;治疗组在此基础上加用双环醇片3 mg/kg·次,2次/d口服;均连用2周,观察效果。结果两组自身比较治疗前后比较谷丙转氨酶、碱性磷酸酶、血清总胆红素、血清总胆汁酸、谷氨酰转肽酶差异有统计学意义(P<0.01);治疗后两组组间比较谷丙转氨酶、碱性磷酸酶、血清总胆红素、血清总胆汁酸、谷氨酰转肽酶差异有统计学意义(P<0.01);治疗组临床疗效显著,与对照组比较差异有统计学意义(P<0.05)。治疗组治疗后血清抗CMVIg M转阴率较对照组高,差异有统计学意义(P<0.05)。结论双环醇联合更昔洛韦治疗婴儿巨细胞病毒感染性肝炎能够在一定程度上降低谷丙转氨酶、碱性磷酸酶、血清总胆红素,降低胆汁酸水平,减轻肝细胞损伤,保护肝细胞,促进肝细胞恢复。

双环醇与多烯磷脂酰胆碱治疗酒精性脂肪肝的临床病理比较

观察双环醇与多烯磷脂酰胆碱治疗酒精性脂肪肝的临床病理差异。55例患者随机分为两组,治疗组29例给予双环醇,对照组26例给多烯磷脂酰胆碱,疗程36周。两组各20例治疗前后肝组织学比较。治疗36周,双环醇组完全应答率50％,部分应答率30％,多烯磷脂酰胆碱组分别为45％和15％,双环醇组在改善ALT、ALP、GGT和肝纤维化积分优于多烯磷脂酰胆碱,双环醇组血清GST—Px治疗后升高,两组治疗后MDA均下降。

30例健康志愿者口服双环醇片剂的药代动力学研究

目的 研究健康志愿者口服双环醇片剂的药代动力学。方法 30名健康志愿者 ,随机分成 2 5、 5 0、10 0mg3个剂量组 ,分别给予单一剂量、多次剂量、餐前、餐后给药 ,用HPLC测定血药浓度 ,用3p97软件进行药代动力学分析。结果 药代动力学符合一房室模型及一级动力学消除规律 ,3个剂量单次给药代动力学参数分别为t( 1/2 )ka(0 .84±0 .6 8)、(0 .33± 0 .0 9)、(1.19± 10 .9)h。t( 1/2 )ke为(6 .2 6± 6 .2 4 )、(6 .17± 2 .0 1)、(4.6 6± 1.2 1)h。Vd/F 为 (45 5 .0 2± 135 .35 )、(6 2 2 .94± 32 5 .37)、(6 88.83± 30 8.14 )L。CL/F为 (93.4 5± 6 7.6 6 )、(83.31± 71.97)、(10 4 .30± 4 5 .76 )L·h- 1。cmax和AUC与剂量成正比。单次和多次口服双环醇片剂的药代动力学参数比较无显著差异。表明在一定剂量范围内 ,体内无蓄积现象。餐前、餐后的cmax分别为 (15 1.2 6± 39.0 0 )和 (2 2 2 .6 4± 4 3.2 2 ) μg·L- 1(P<0 .0 1) ,但AUC0～∞ 无明显差异 ,这可能与双环醇片剂的脂溶性有关。结论 双环醇片剂的药代动力学符合线性动力学特征 。

微生态制剂联合双环醇对非酒精性脂肪肝的临床疗效及对肝纤维化、血脂水平、血清炎症因子、TGF-β1的影响

目的:探讨微生态制剂联合双环醇对非酒精性脂肪肝(NAFLD)的临床疗效及对肝纤维化、血脂、血清炎症因子、转化生长因子β1(TGF-β1)的影响。方法:选取符合要求的NAFLD患者106例,分为对照组和病例组各53例。对照组给予常规护肝和双环醇;病例组在对照组治疗的基础上给予微生态制剂双歧杆菌三联活菌。两组治疗6周,观察两组治疗后的临床疗效、肝纤维化、血清炎症因子、TGF-β1等变化。结果:病例组的总有效率高于对照组,差异有统计学意义(χ2=4.970,P=0.026)。两组治疗后ALB、HDL较前升高,ALT、AST、TBIL、LN、HA、PCⅢ、CIV、TC、TG、LDL、IL-6、TNF-a、hs-CRP、TGF-β1较前降低,同组治疗前后比较,差异具有统计学意义(P<0.05);且病例组肝功能、肝纤维化、血脂水平、血清炎性因子、TGF-β1改善优于对照组,差异有统计学意义(P<0.05)。病例组不良反应发生率低于对照组,差异无统计学意义(χ2=1.093,P=0.296)。结论:微生态制剂联合双环醇治疗NAFLD临床疗效确切,可以明显改善肝功能,降低血脂,减轻炎症刺激和肝纤维化程度,安全性较好。

五味子制剂对大鼠他克莫司血药浓度的影响及对肝损伤的防护作用

目的:探讨临床常用的两种五味子制剂五酯胶囊和双环醇对大鼠免疫抑制剂他克莫司血药浓度的影响及对肝损伤的防护作用。方法:将55只大鼠随机分成4组,空白对照组10只,FK506单独给药组,FK506+五酯胶囊联合给药组,FK506+双环醇联合给药组,每组各15只。分别以FK506 1mg/kg,五酯胶囊11.25mg/kg,双环醇200mg/kg,每日1次连续灌药21d,给药后第7、14、21天禁食8h后采血检测FK506浓度和肝功能,处死大鼠取肝脏行病理学检查。结果:未加五味子制剂的FK506单药组血药浓度上升缓慢,加用五酯胶囊组和双环醇组均具有提高FK506血药浓度的作用。五酯胶囊组他克莫司血药浓度上升比较快,与对照组相比给药7d差异即出现统计学意义(F=11.043,P=0.002),14d(F=98.167,P=0.000)和21d(F=57.457,P=0.000),差异更加显著。但双环醇组与五酯胶囊组相比各时间点差异均无统计学意义。双环醇保肝作用明显,与对照组相比,给药7d后ALT显著降低,差异具有统计学意义(F=12.83,P=0.001),给药14d(F=11.58,P=0.002)和21d(F=22.27,P=0.000)差异更加显著。五酯胶囊组降低ALT的作用弱起效慢,7、14、21d与对照组相比均无统计学意义。双环醇组能使白蛋白(ALB)保持在较高水平,各时间点与对照组相比差异具有统计学意义(P<0.05)。FK506对肝细胞的损伤发生在用药早期,在组织学表现为肝细胞水肿、变性和炎症细胞浸润。结论:五酯胶囊和大剂量双环醇均具有提高大鼠他克莫司血药浓度的作用,并且起效较快;FK506对肝细胞损伤发生在用药早期,双环醇具有预防FK506所致肝损伤的作用。