多烯磷脂酰胆碱对高脂饮食诱导的肥胖小鼠代谢紊乱的影响

目的研究多烯磷脂酰胆碱改善高脂饮食诱导的代谢紊乱和脂肪肝作用机制。方法将32只C57BL/6小鼠随机分为空白组、对照组、模型组和实验组。空白组每周2次喂食低脂饮食并腹膜内注射10%葡萄糖200μL;对照组每周2次喂食低脂饮食并腹膜内注射含有多烯磷脂酰胆碱(PPC)20μg的10%葡萄糖溶液200μL;模型组每周2次喂食高脂肪饮食并腹膜内注射10%葡萄糖200μL;实验组每周2次喂食高脂肪饮食并腹膜内注射含有PPC 20μg的10%葡萄糖溶液200μL。称取小鼠体质量,用血糖测试条测量血糖、分析胰岛素抵抗;用生化分析血清和肝组织中三酰甘油(TG)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)、谷草转氨酶(GOT)、谷丙转氨酶(GPT)的水平;用酶联免疫吸附测定(ELISA)法检测肝肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-8炎症因子水平。结果空白组、对照组、模型组及实验组小鼠血清TG水平分别为(0.15±0.01)、(0.11±0.01)、(0.21±0.01)和(0.12±0.01)mmol·L^(-1),LDL水平分别为(0.41±0.01)、(0.25±0.01)、(0.71±0.02)和(0.49±0.01)mmol·L^(-1),HDL水平分别为(3.04±0.06)、(3.17±0.07)、(2.03±0.05)和(3.72±0.01)mmol·L^(-1),GOT水平分别为(30.30±0.89)、(31.39±1.18)、(43.04±2.82)和(25.64±0.72)mmol·L^(-1),GPT水平分别为(9.15±0.45)、(7.39±1.88)、(12.87±1.81)和(7.96±1.64)mmol·L^(-1),空腹血糖水平分别为(4.97±0.08)、(6.08±0.18)、(8.12±0.20)和(7.29±0.02)mmol·L^(-1),空腹胰岛素水平分别为(6.52±1.11)、(5.45±0.28)、(54.83±4.32)和(30.55±2.73)mU·L^(-1),肝组织TNF-α水平分别为(3.98±0.63)、(3.95±0.98)、(20.55±4.71)和(15.28±1.73)pg·g^(-1),IL-6水平分别为(18.93±8.56)、(17.64±3.29)、(59.40±4.63)和(37.54±7.33)pg·g^(-1),IL-8水平分别为(67.16±12.37)、(59.44±3.58)、(198.40±9.27)和(132.10±7.04)pg·g^(-1)。实验组上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论多烯磷脂酰胆碱可能通过介导抑制TNF-α、IL-6、IL-8炎症因子的表达,抑制炎症对肝组织的浸润继而改善代谢紊乱。

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients:A Randomized Controlled 48-Week Trial

Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil(ADV)plus Chinese medicine(CM)therapy,namely Tiaogan Jianpi Hexue(调肝健脾和血)and Tiaogan Jiedu Huashi(调肝解毒化湿)fomulae,in hepatitis B e antigen(HBeAg)-positive Chinese patients.Methods:A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group(EG,received ADV plus CM)and control group(CG,received ADV plus CM-placebo)for 48 weeks.The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12,24,36,48,respectively.Secondary endpoints including liver functions(enzymes and bilirubin readings)were evaluated every 4 weeks at the beginning of week 24,36,and 48.Routine blood,urine,and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations.Adverse events(AEs)were documented.Results:The combination therapy demonstrated superior HBeAg loss at 48 weeks,without additional AEs.The full analysis population was 560 and 280 in each group.In the EG,population achieved HBeAg loss on week 12,24,36,and 48 were 25(8.90%),34(12.14%),52(18.57%),and 83(29.64%),respectively;the equivalent numbers in the CG were 20(7.14%),41(14.64%),54(19.29%),and 50(17.86%),respectively.There was a statistically significant difference between two groups on week 48(P<0.01).No additional AEs were found in EG.Subgroup analysis suggested different outcomes among treatment patterns.Conclusion:Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy.The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile(ChiCTR-TRC-11001263).

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B:Study Protocol for a Multi-Center,Double-Blind Randomized-Controlled Trial

Background： The domestic prevalence of chronic hepatitis B （CHB） in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot（s）ide analogues （NUCs） anti-hepatitis B virus （HBV） therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine （CHM） is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule （调肝益脾颗粒, TGYP） or Tiaogan-Jianpi-Jiedu Granule （调肝健脾解毒颗粒, TGJPJD） plus entecavir tablet （ETV） was superior over ETV monotherapy in enhancing HBeAg loss rate. Methods： The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1：1 ratio via central randomization system： experimental group （EG） and control group （CG）. Subjects in EG received CM formulae （TGYP or TGJPJD, 50 g per dose, twice daily） plus ETV tablet （or ETV placebo） 0.5 mg per day in the first 24 weeks （stage 1）, and CHM granule plus ETV tablet （0.5 mg per day） from week 25 to 108 （stage 2）. Subjects in CG received CHM Granule placebo plus E＇IV tablet （0.5 mg per day） for 108 weeks throughout the trial. The assessments of primary outcomes （HBV serum markers and HBV-DNA） were conducted by a third-party College of American Pathologists （CAP） qualified laboratory. Adverse effects were observed in the hospitals of recruitment. Discussion： The study was designed to compare the curative effect of CM plus E＇IV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as ＂a valuable endpoint＂. We believe this trial could provide a reliable status for patients＇ ＂joumey＂ towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry （No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23）.