疏肝健脾方药对非酒精性脂肪性肝病大鼠肝组织UCP2 mRNA及蛋白表达的影响

目的观察疏肝健脾方药对非酒精性脂肪性肝病（non—alcoholic fatty liver disease,NAFLD）大鼠肝组织解偶联蛋白2（uncoupling protein 2,UCP2）mRNA及蛋白表达的影响,初步探讨疏肝健脾方药治疗NAFLD的作用机制。方法采用高脂饲料喂养12周复制雄性SD大鼠NAFLD模型,将模型大鼠分为疏肝纽、健脾组、疏肝健脾综合组（综合组）、三七脂肝丸组（三七组）、模型组,各组给予相应治疗8周。测定各组大鼠血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇含量。采用RT—PCR方法检测肝组织UCP2 mRNA的表达,免疫组织化学方法检测肝组织中UCP2蛋白活性变化。结果与正常组比较,模型组大鼠肝组织中UCP2 mRNA表达水平显著升高（P〈0．05）;与模型组比较,疏肝组、健脾组和综合组UCP2 mRNA表达水平显著下降（P〈0．05）。模型组肝组织UCP2蛋白表达水平显著升高;与模型组比较,各用药组UCP2蛋白表达水平均显著下调（P〈0．01）。结论疏肝健脾方药可使NAFLD大鼠肝组织中UCP2基因和蛋白表达水平降低。     

疏肝健脾方药对非酒精性脂肪性肝病大鼠肝细胞PI3K p85α蛋白表达的影响

目的观察疏肝健脾方药对非酒精性脂肪性肝病（NAFLD）大鼠肝细胞磷脂酰肌醇-3-激酶p85α（PI3K p85α）表达的影响。方法以高脂饮食12周建立大鼠NAFLD模型后,造模组大鼠再随机分为模型组、疏肝组、健脾组、综合组和自然恢复组等5组。治疗组分别给予相应药物灌胃,其他组给予等量蒸馏水灌胃,模型组继续高脂饮食,其余均予基础饲料喂养。治疗8周后,用3%戊巴比妥腹腔麻醉,腹主动脉取血,全自动生化仪检测血脂及肝功,稳态模型法评价胰岛素抵抗程度,光镜下观察各组肝脏病理改变,免疫组化方法检测肝细胞内PI3K p85α蛋白的表达情况。结果与模型组相比,药物治疗各组及自然恢复组肝脏脂变程度明显减轻,肝功、血脂、胰岛素抵抗均有显著改善（P〈0.05或P〈0.01）,肝细胞内PI3K p85α蛋白的表达明显减少（P〈0.05）。与自然恢复组相比,药物治疗各组肝功、血脂、血糖的改善无显著差异,但肝脏脂变程度减轻,胰岛素抵抗指数明显下降（P〈0.05）,肝细胞内PI3K p85α蛋白的表达显著降低（P〈0.05）。结论疏肝健脾方药对高脂饮食诱导的大鼠NAFLD有较好的治疗作用,其机制可能是与其降低肝细胞PI3K p85α的表达有关。     

Experimental study on effect of renal failure granule in treating uremia

Objective: To observe the efficacy of Renal Failure Granule (RFG) in treating uremia and explore its mechanism. Methods: Platt's method was used to establish the chronic renal failure model. Forty-eight rats were divided into normal group, model group, Jiangzhuo recipe (降浊方) group, Fuzheng recipe (扶正方) group, RFG group and aldehyde-oxygen encapsulated starch group, 8 rats in each group, to observe the effects of RFG on serum creatinine (SCr), blood urea nitrogen (BUN), plasma calcium (Ca), plasma phosphorus (P), parathyroid hormone (PTH), middle molecular substance (MMS), methylguanidine (MG), guanidinosuccinic acid (GSA) and other parameters. Results: Comparison of SCr and BUN changes after medication for 30 and 60 days, the RFG group, the Fuzheng recipe group and the Jiangzhuo recipe group, with the aldehyde-oxygen encapsulated starch group or model group, demonstrated that the difference was significant (P<0.05, P<0.01), For PTH, Ca, P, MMS, MG and GSA, RFG was clearly different with the model group (P<0.05, P<0.01). Jiangzhuo recipe and Fuzheng recipe group also were variously efficacious in above-mentioned parameters. Conclusions: RFG can retard the development of uremia, and its mechanism may be related to the decrease of uremic toxin.     

糖代谢异常对大鼠肝脏组织中巨噬细胞移动抑制因子及C-Jun氨基端激酶表达水平的影响

目的 观察巨噬细胞移动抑制因子（MIF）和C-Jun氨基端激酶（JNK）在糖代谢异常大鼠肝脏组织中表达水平的变化，探讨糖代谢异常合并非酒精性脂肪肝（NAFLD）的病理机制。方法 将60只大鼠随机分为糖耐量受损（IGT）模型组（n=20）、2型糖尿病（T2DM）模型组（n=20）、IGT对照组（n=10）及T2DM对照组（n=10），高脂饲料喂养复制IGT大鼠模型，高脂饲料喂养加腹腔注射小剂量链脲佐菌素（STZ）制备T2DM大鼠模型，采用TUNEL法检测各组大鼠肝脏细胞凋亡；实时荧光PCR 技术检测肝脏组织中MIF mRNA的表达； Western Blot方法检测肝脏组织中MIF 、Caspase-3、JNK蛋白表达及磷酸化JNK （p-JNK）的表达。结果 IGT大鼠及T2DM大鼠肝组织凋亡细胞明显增多；IGT组和T2DM组肝组织MIF基因表达较各自对照组明升高（P<0.01），MIF 、Caspase-3、JNK蛋白表达及JNK磷酸化水平也明显升高（P<0.05或P<0.01）；与IGT组相比，T2DM组Caspase-3、MIF、JNK蛋白表达水平明显降低（P<0.01），而JNK磷酸化水平是明显升高（P<0.01）。结论 糖代谢异常大鼠肝组织的损伤以及非酒精性脂肪肝的发生可能与肝组织MIF 、Caspase-3、JNK表达水平的升高及JNK磷酸化水平的增强有关。     

Antifibrotic Effect of Total Flavonoids of Astmgali Radix on Dimethylnitrosamine-Induced Liver Cirrhosis in Rats

Objective: To study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR). Methods: Fifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week. Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low- and high-TFA groups, respectively. At the end of the experiment blood and liver samples were collected. Serum liver function and liver tissue hydroxyproline content were determined. hematoxylin-eosin (HE), Sirus red and immunohistochemical stainings of collagen Ⅰ, smooth muscle actin (α-SMA) was conducted in paraffinembedded liver tissue slices. Real time polymerase chain reaction (PCR) was adopted to determine PPARγ, UCP2 and FXR mRNA levels. Western blot was adopted to determine protein levels of collagen Ⅰ, α-SMA, PPARγ, UCP2 and FXR. Results: Compared with the model group, TFA increased the ratio of liver/body weight (low-TFA group P<0.05, high-TFA group P<0.01), improved liver biochemical indices (P<0.01 for ALT, AST, GGT in both groups, P<0.05 for albumin and TBil in the high-TFA group) and reduced liver tissue hydroxproline content (P<0.01 in both groups) in treatment groups significantly. HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition, alleviated formation and extent of liver pseudolobule. Collagen Ⅰ and α-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group. TFA could increase PPARγ, it regulated target UCP2, and FXR levels significantly compared with the model group (in the low-TFA group all P<0.05, in the high group all P<0.01). Conclusions: TFA could improve liver function, alleviate liver pathological changes, and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis. The antifibrotic effect of TFA was through regulating PPARγ signal pathway and the interaction with FXR.     

舒脉胶囊对血管紧张素Ⅱ诱导的血管平滑肌细胞迁移的影响

目的观察舒脉胶囊及其拆方药物血清对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的血管平滑肌细胞(vascular smooth muscle cells,VSMC)迁移的影响。方法采用组织贴块法进行VSMC培养,AngⅡ10-7 mol/L作为刺激因子,将药物血清分为舒脉胶囊全方组、活血化瘀拆方组和补脾益肾拆方组,测微尺测量细胞迁移的距离,免疫组织化学法测量基质金属蛋白酶-2(metalloproteinase-2,MMP-2)的表达情况。结果与AngⅡ组比较,舒脉胶囊全方组、活血化瘀拆方组细胞迁移距离显著减小(P<0.01),MMP-2表达减少(P<0.01),其中舒脉胶囊全方组细胞迁移距离显著小于活血化瘀拆方组(P<0.01)。结论舒脉胶囊通过抑制MMP-2的表达而抑制VSMC迁移,全方作用优于拆方。     

Study on treatment of uloerative colitis with Liver-Qi stagnation by nourishing the Liver

Objective: To study the links between stagnation of the Liver-Qi and the pathogenesis of ulcerative colitis (UC) were studied clinically and experimentally.Methods: Using the principle of nourishing the Liver in the treated group and invigorating the Spleen in the control group.Results: The effective rate was 96% in the treated group and 82% in the control group, and the difference was significant (P<0.05); the formation rate of E rosettes and the transformation rate of lymphocytes were significantly raised in the two groups compared with the pre-treatment period, and the rate of adjusting dysfunction of vegetative nerve system in the treated group was evidently higher than that in the control group (P < 0.01). The level of intestinal styrenated phenol (SP) and vasoactive intestinal polypeptide (VIP) of UC model were determined in rats, and results showed that the level of SP and VIP significantly increased in the UC model group. They were markedly lowered in the treated group compared with model group (P < 0. 01) and there was significant difference from the control group (P<0.01).Conclusion: Wei Chang Ning , a drug to nourish the Liver, had the action of regulating neurological-endocrinological (gastrointestinal hormone)-immunological system.     

Effect and Mechanisms of Gong-Tone Music on the Immunological Function in Rats with Liver (Gan)-Qi Depression and Spleen (Pi)-Qi Deficiency Syndrome in Rats

Objective: To investigate the effects and mechanisms of Gong-tone music on the immunological function in rats with the Chinese medicine syndrome of Liver (Gan)-qi stagnation and Spleen (Pi)-qi deficiency (LSSD). Methods: Twenty five male Wistar rats of SPF grade were randomly divided into 5 groups: normal group, model group, Xiaoyao Powder (逍遥散) group, Gong-tone group and combined group (the combination of Gong-tone and Xiaoyao Powder), with 5 rats in each group. The rat model for the Chinese medicine syndrome of LSSD was induced by chronic bandage and irregular diet. The course of treatment was 21 days. After the treatment, the levels of serum gastrin and IgG were detected by enzyme-linked immunoabsorbent assay (ELISA). Phagocytosis of macrophages was detected by the neutral red uptake assay and T cell proliferation was investigated by 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The serum gastrin, macrophage phagocytosis, IgG level and proliferation ability of T cells in the model group were significantly decreased compared with those in the normal group (P<0.05). Compared with those in the model group, the serum levels of gastrin, macrophage phagocytosis, IgG level and proliferation ability of T cells in Gong-tone, Xiaoyao Powder, and combined groups were significantly increased (P<0.05). The combined group was superior to either Gong-tone group or Xiaoyao Powder group. Conclusion: Gong-tone music may upregulate the immunological function and play a role in adjuvant therapy in the Chinese syndrome of LSSD.     

Effect of oxymatrine on hepatic gene expression profile in experimental liver fibrosis of rats

Objective:To investigate the effects of oxymatrine on hepatic gene expression profile in a rat model of liver fibrosis.Methods:Forty healthy male SD rats were randomly divided into three groups,a normal group（n=8）,a model group（n=16）,and an oxymatrine treatment group（n=16）.Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride（CCI₄）.The rats in the treatment group received oxymatrine via celiac injection at a dosage of 40 mg/kg once a day at the same time.The rats in the model and normal groups received saline at the same dosage via celiac injection.Serum levels of aspartate aminotransferase （AST）,alanine transarninase（ALT）,alkaline phosphatase（AKP）,hyaluronic acid（HA）,and laminin（LN）were assayed.The deposition of collagen was observed with HE and Masson staining.Effect of oxymatrine on hepatic gene expression profile was detected by oligonucleotide microarray analysis with Affymetrix gene chip rat U230A. Quantitative real-time polymerase chain reaction（QRT-PCR）was carried out to confirm the expression changes of six genes.Results:Oxymatrine significantly improved liver function,lowered serum levels of HA and LN,and decreased the degree of liver fibrosis,compared with the model group（P<0.05）.A total of 754 differentially expressed genes were identified by gene chip between the model group and the normal group,among which 438 genes increased and 316 genes decreased over two folds.Compared with the model group,86 genes were downregulated markedly in the oxymatrine group（P<0.05）,including collagen I and other genes related to extracellular material（ECM）,integrin signal transduction genes,early growth response factor genes,and proinflammatory genes;28 genes were upregulated significantly（P<0.05）,including cytochrome P450（CYP450） superfamily genes,glycolipids metabolism and biological transformation related genes.Six genes were confirmed with QRT-PCR,consistent with the result from microarray.Conclusion:Oxymatrine could affect the expression of many functional genes and may be useful in the prevention and treatment of liver fibrosis.     

补肾和柔肝中药对C57黑鼠膝骨关节炎滑膜中COMP基因表达的影响

目的：研究补肾和柔肝中药对C57黑鼠膝骨关节炎滑膜中软骨寡聚基质蛋白（COMP）基因表达的影响。方法：将7周龄C57黑鼠随机分为空白组、模型组、补肾组、柔肝组、芬必得组,雌雄各半。除空白组外,其余各组先进行4周跑步造模,再分别予生理盐水、补肾方（密骨胶囊）、柔肝方（养血软坚胶囊）、芬必得灌胃。给药4周后取材,应用Trizol法抽提总RNA,RT-PCR技术半定量检测膝关节滑膜中COMP基因表达,采用天能GIS凝胶图像处理系统分析各组表达灰度值。结果：模型组与空白组相比,滑膜中COMP基因表达明显升高（P〈0.01）,各药物组与模型组比较,滑膜中COMP基因表达明显降低（P〈0.05）;补肾组与柔肝组比较,滑膜中COMP基因表达明显升高（P〈0.01）,两者有显著性差异。结论：补肾和柔肝中药均可以下调C57黑鼠膝骨关节炎滑膜中COMP基因的表达水平,可以延缓滑膜的增生和纤维化,减少滑膜分泌炎症介质和软骨降解酶,对骨关节炎有明显的防治作用,且柔肝中药明显好于补肾中药。     

玉屏风散对慢性支气管炎大鼠的抗炎及免疫调节作用

Objective: To investigate the anti-inflammatory and immunoregulatory effects of Yupingfeng (玉屏风, YPF) Powder and its components in rats. Methods: A rat chronic bronchitis (CB) model was developed using lipopolysaccharide (LPS) combined with bacillus Calmette Guerin (BCG). YPF, simple recipe Astragalus membranaceus (Fisch.) Bge (AM) and Astragalus membranaceus (Fisch.) Bge plus rhizome of Atractylodes macrocephala Koidz (AM+RA) decoction were administered (intragastric administration, once a day for 21 days) to rats, to prevent and treat CB. Immunoregulatory and anti-inflammatory effects of YPF, AM and AM+RA were tested by serum pharmacology in vitro on splenic lymphocytes of normal rats and alveolar macrophages of CB rats. Results: Inflammation in the pulmonary tissue and the bronchus of CB rats was significantly reduced in the YPF-treatment groups, AM and AM+RA groups demonstrating the efficacy of YPF. Serum samples collected at different times from rats after administration of YPF, AM and AM+RA demonstrated increased proliferation of splenic lymphocytes with area under the effect curve (AUE) of 552.6%, 336.3% and 452.0%, respectively. Treatment of alveolar macrophages with serum samples in YPF, AM or AM+RA group inhibited interleukin-8 (IL-8) in the cell culture media, and the effect was much better in the YPF group compared with AM or AM+RA group, with a higher maximal effect (Emax, P<0.05) and larger AUE (P<0.01 and P<0.05). Moreover, serum from rats treated with AM or AM+RA had similar efficacy, while the efficiency was lower than that treated with YPF. Conclusion : YPF demonstrated anti-inflammatory and immunoregulatory effects in a rat model of CB, and time-dependent relationships were demonstrated in vitro.     

Study on the anti-liver fibrosis effect of benefit liver granule and its mechanism in rats

Objective

To explore the effect of Benefit Liver Granule (BLG), a traditional Chinese medical preparation, in antagonizing liver fibrosis and its possible mechanism.

Methods

Carbon tetrachloride was used to establish the experimental liver fibrosis model of rat. The model rats were randomly divided into 4 groups and BLG, Astragalus (As), Salvia (Sa) and normal saline (for control) respectively were given to them by gastrogavage. Changes of serum alanine transaminase (ALT), aspartate aminotransferase (AST), transforming growth factor α(TGF-α), interleukine-6 (IL-6), liver content of hydroxyproline (Hyp), superoxide dismutase (SOD), malonyldialdehyde (MDA) as well as liver pathology after treatment were observed. A normal control group was also established for control.

Results

Pathological examination showed that in the saline group, the structure of normal hepatic lobuli was destroyed with swelled liver cells, focal necrosis, extensive fatty degeneration, and focal inflammatory cell infiltration. Small amounts of proliferated fiber tissue were found in the intra-lobular area, peri-central vein area, portal area and limiting plate area, and formation of pseudolobuli was also seen. In the 3 treated groups, the serum ALT, AST, TGF-α and IL-6 as well as liver content of Hyp, and MDA were lower and SOD were higher than those in the control group significantly,P<0.05 orP<0.01.

Conclusion

BLG, As and Sa have the action of anti-liver fibrosis, while BLG has the best effect. The mechanisms are probably related to their effects in regulating TGF-α and IL-6, reducing collagen fiber synthesis, promoting free radical scavenge and anti-lipid peroxidation.     

补肾化痰祛瘀法对血管性痴呆大鼠认知功能的保护作用

目的研究补肾化痰祛瘀方对血管性痴呆（VaD）大鼠认知功能的改善作用。方法在缺糖缺氧培养条件下,观察补肾化痰祛瘀方血清对体外培养的海马神经元的保护作用。用双侧颈总动脉永久性结扎法（2VO）制备VaD大鼠模型,造模前予灌胃治疗,Morris水迷宫测试治疗后VaD大鼠认知功能的改善情况,TUNEL染色测定各组大鼠海马脑组织内细胞凋亡的变化。免疫组织化学方法检测Bcl-2、Bax蛋白表达。结果在缺糖缺氧培养条件下,体外培养海马神经元出现大量的细胞凋亡,而预先加入补肾化痰祛瘀方的血清进行处理后,细胞凋亡率明显下降。补。肾化痰祛瘀方灌胃治疗的VaD大鼠,与未予治疗的VaD大鼠组相比,治疗组大鼠找到平台的潜伏期缩短（P〈0．01）,穿越平台次数增多（P〈0．01）;与痴呆组相比,补肾化痰祛瘀方治疗组大鼠脑组织海马区凋亡细胞数明显减少,抗凋亡基因Bcl-2蛋白表达显著增加,凋亡基因Bax蛋白表达降低,差异有统计学意义（P〈0．01）。结论补肾化痰祛瘀方对大鼠体外培养和脑组织内海马神经元具有神经保护作用,补肾化痰祛瘀方治疗可以明显改善VaD大鼠的认知功能。     

Effects of extracts from soothing-liver and invigorating-spleen formulas on the injury induced by oxidative stress in the hepatocytes of rats with non-alcoholic fatty liver disease induced by high-fat diet

OBJECTIVE

To investigate effects of the extracts from soothing-liver and invigorating-spleen formulas on the injury due to oxidative stress, mediated by the Nuclear factor-like 2 (Nrf2)-Antioxidant response element (ARE) pathway, in the hepatocytes of rats with non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet.

Ethanol Extract of Phellinus merrillii Protects against Diethylnitrosamine- and 2-Acetylaminofluorene-Induced Hepatocarcinogenesis in Rats

Objective: To study whether the ethanol extract of Phellinus merrillii (EPM) has chemopreventive potential against liver carcinogenesis. Methods: Thirty male Spraque-Dawley rats were randomly divided into control group, EPM control group, hepatocarcinoma control group, low-dose EPM group and high-dose EPM group, 6 in each group. Using the Solt and Farber protocol in a rat model of hepatocarcinogenesis, the chemopreventive effect of EPM on diethylnitrosamine (DEN)-initiated, 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH)-promoted liver carcinogenesis in rats was evaluated. Basic pathophysiological and histological examinations, together with the serum levels of glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT) and gamma-glutamyl transpeptidase (γ-GT) were measured. Results: Treatment of EPM at the concentration of 2 g/kg body weight in the diet for 8 weeks clearly prevented the development of carcinogenesis and reduced the levels of sGOT, sGPT, and serum γ-GT of rats as compared with the hepatocarcinoma control group (P<0.05 or P<0.01). These phenotypes were accompanied by a significant increase in natural killer cell activity. Conclusion: EPM showed a strong liver preventive effect against DEN+2-AAF+PH-induced hepatocarcinogenesis in a rat model.     

大小承气汤制作大鼠脾虚肝癌模型的比较

目的 探索大小承气汤为基础的多因素大鼠脾虚模型和脾虚肝癌模型的制作方法和成模差别。方法 采用苦寒泻下、寒湿环境、劳累、隔天禁食的方法制作脾虚大鼠模型,其中苦寒泻下因素采用大承气汤和小承气汤分别干预;Walker256大鼠肝癌细胞经裸鼠皮下增殖后移植入大鼠肝脏,制作肝癌模型。大鼠随机分为正常组、空白肝癌组、大承气汤组、小承气汤组,每组15只3周龄Wistar雄性大鼠,脾虚因素干预30天后恢复7天制作肝癌模型并观察35天。实验过程中观察动物脾虚程度、体重变化、成瘤情况、生存时间等。结果 大、小承气汤组动物在脾虚造模过程中相对于对照组,体重增长受到明显抑制P<0.01,脾虚造模前20天大承气汤组动物体重均高于小承气汤组,P<0.05,之后二者无差别P>0.05。大、小承气汤组动物平均脾虚积分高于空白肝癌组,小承气汤组最高,P<0.01。肝癌模型总成瘤率91.1%,空白肝癌组为80%,大、小承气汤组均为93.3%。小承气汤组大鼠平均生存天数小于肝癌组和大承气汤组,P<0.01和0.05。生存分析提示脾虚积分高的肝癌模型和小承气汤组肝癌模型的生存能力明显下降,P<0.05。结论 小承气汤在多因素制作脾虚模型过程中致脾虚作用比大承气汤强,脾虚明显是肝癌模型预后不良的重要因素。     

Hypolipidaemic and antioxidant effect of Enicostemma littorale Blume

Objective

To investigate the hypolipidaemic and antioxidant effects of aqueous leaf extract of Enicostemma littorale (E. littorale) Blume (Ens) against ethanol induced hepatic injury in albino rats.

Methods

Male albino rats of six numbers in each group were undertaken for study. Hypolipidaemic and antioxidant effect of E. littorale Blume (Ens) aqueous leaf extract at a dosage of 250 mg/kg bw was evaluated.

Results

Levels of serum and tissue cholesterol, triglycerides and free fatty acids were elevated and levels of tissue thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide were increased in ethanol treated rats. The activity levels of liver antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione-s-transferase (GST) were decreased. After adiminstration of extract of E. littorale Blume, levels of cholesterol, triglycerides and free fatty acids were decreased in serum and liver tissue, levels of TBARS and lipid hydroperoxide were decreased, and liver antioxidant enzymes were increased in liver tissue.

Conclusions

It can be concluded that the aqueous leaf extract of E. littorale Blume (Ens) has potent restorative effect on hyperlipidaemic and oxidative stress.     

Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced Cirrhotic Rats

Objective: To evaluate the preventive effect of salvianolate(Sal B) on glucose metabolism disorders of dimethylnitrosamine(DMN)-induced cirrhotic rats. Methods: Fifty-five Wistar rats were randomly divided into a control group(n=10) and a cirrhotic group(n=45) according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups(n=15), respectively. Rats in the model group were given saline, two treatment groups were given Sal B(50 mg/kg), metformin(150 mg/kg) respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test(OGTT), and fasting plasma glucose(FPG), fasting insulin(FINS), hepatic glycogen, hydroxyproline(HYP) and liver function were detected at the end of the treatment. Area under the curve(AUC) for OGTT was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining(HE), Sirius Red staining and Masson's trichrome staining, respectively. Hepatic expression of α-smooth muscle actin(α-SMA) and collagen(Col Ⅰ) were evaluated by immunohistochemical staining. Results: Compared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate(GIR), FPG, FINS levels and hepatic glycogen at the end of administration(P0.05 or P0.01). Meanwhile, Sal B significantly decreased AUC for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level(P0.05 or P0.01). Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of α-SMA and Col Ⅰ in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis(P0.05). Metformin increased insulin sensitivity more potently than Sal B(P0.05). Conclusions: Sal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.     

Antipyretic Effect of Herba Ephedrae-Ramulus Cinnamomi Herb Pair on Yeast-Induced Pyrexia Rats: A Metabolomics Study

Objective

To investigate the antipyretic mechanism of Herba Ephedrae (Eph)-Ramulus Cinnamomi (RC) herb pair on yeast-induced pyrexia in rats.

Methods

Totally 30 qualified male SD rats were randomly assigned to the normal control (NC) group, the pyrexia model (model) group, the Eph, RC and Eph-RC treatment groups by a random digital table, 6 rats in each group. Each rat received a 20% aqueous suspension of yeast (10 mL/kg) except the NC group. The 3 treatment groups were administered 8.1, 5.4 and 13.5 g/kg Eph, RC and Eph-RC respectively at 5 and 12 h after yeast injection, the NC group and the model groups were administered equal volume of distilled water. Rectal temperatures were measured at 0, 6, 8, 10, 12, 15, 18, 24 and 30 h and urine was collected prior to yeast injection and at 6, 10, 18, 24, 30, and 36 h after yeast injection. Then urine metabolomic profiling by gas chromatography tandem mass spectrometry, coupled with multivariate statistical analysis and pattern recognition techniques were used to explore the antipyretic effects of Eph-RC. Partial least squares discriminate analysis was used to analyze the metabolomics dataset including classification and regression in metabolomics plot profiling.

Results

Compared with the NC group, rectal temperatures were significantly higher in the model group (P<0.01), while 3 treatment groups decreased significantly compared with the model group (P<0.05 or P<0.01). Rectal temperatures of Eph-RC-treated rats started to go down at 6 h, and markedly decreased at 8, 12, 15, 18 and 24 h (P<0.05 or P<0.01), while those of the Eph and RC groups had decreased firstly at 8 h and were markedly lower at 12 h (P<0.05 or P<0.01). Seventeen potential biomarkers related to pyrexia were confirmed and identified, including pyruvic acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic acid, citrate and so on. Eight potential alterations of metabolic pathways including phenylalanine metabolism, citrate cycle, tryptophan metabolism, biosynthesis of valine, leucine and isoleucine, were identified in relation to the antipyretic effects of Eph-RC using MetPA software.

Conclusion

The antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved correction of perturbed amino acid, fatty acid, and carbohydrate metabolism according to the metabolic pathway analysis with MetPA.