胆宁片对实验性急慢性肝损伤的保护作用

目的：研究胆宁片对实验性小鼠急性肝损伤预防作用，及对大鼠慢性肝损伤的预防和治疗作用。方法：分别用D-氨基半乳糖和四氯化碳复制小鼠急性肝损伤和大鼠慢性肝损伤模型，检测小鼠和大鼠血清谷草转氨酶（AST）和谷丙转氨酶（ALT）的改变，观察胆宁片对大鼠血清总蛋白、白蛋白、A／G的影响、同时观察肝脏病理学改变。结果：胆宁片可明显抑制D-氨基半乳糖和四氯化碳引起的ALT、AST升高（P〈0．05或P〈0．01）；可显著升高四氯化碳引起的血清总蛋白和白蛋白含量降低（P〈0．05或P〈0．01）；肝脏病理组织学检查显示胆宁片可减轻肝细胞脂肪变性程度和纤维化程度。结论：胆宁片对小鼠D-氨基半乳糖急性肝损伤有较好的保护作用，对四氯化碳所致大鼠慢性肝损伤有一定的预防及治疗作用。     

七丹胶囊对CCl4致小鼠急性肝损伤的保护作用

目的 采用体外细胞培养和体内试验,探讨三七总皂苷与丹参总酚酸不同配比的药效作用,以确定二者的最佳配伍比例.方法 研究三七总皂苷与丹参总酚酸不同配比对体外细胞的培养和对CCl4诱导的小鼠急性肝损伤的影响.结果 三七总皂苷和丹参总酚酸对CCl4诱导的小鼠急性肝损伤有明显的保护作用,二者配伍后作用增强,以三七总皂苷-丹参总酚酸为5:1时的保护作用最强.结论 两者均有保肝、抑制成纤维细胞增殖的作用,配伍后作用增强,毒性降低.     

三七及其有效活性成分在保肝方面的研究进展

三七为常用中药,在《本草纲目》中有详细记载。三七具有止血、抗血栓、促进造血、抗炎、保肝、抗肿瘤、镇痛等作用。本文对三七及其有效活性成分对肝的保护作用机制(改善肝纤维化、改善肝脏微循环、酒精性肝损伤保护机制、抗急性肝损伤作用、三七总皂苷对肝的影响机制等)的相关研究进展作一综述,并对其前景进行展望,为临床治疗肝脏疾病提供依据和参考。     

珠子肝泰对实验性慢性肝损伤的影响

目的观察珠子肝泰合剂对慢性肝损伤的作用。方法采用适量四氯化碳(CCl4)多次注射造成慢性肝损伤模型,给予同剂量的珠子肝泰合剂,测定血清转氨酶(ALT、AST)、胆碱酯酶(CHE),肝组织匀浆ALT与CHE、谷胱苷肽(GSH)、丙二醛(MDA)、碱性磷酸酶(ALP),HE染色观察肝组织形态学。结果珠子肝泰合剂能有效地降低CCl4所致慢性肝损伤大鼠血清与匀浆ALT,升高血清CHE,降低GSH与MDA,HE显示受损的肝细胞有用药后较好的恢复作用。结论珠子肝泰合剂对皮下注射四氯化碳致大鼠慢性肝损伤具有显著的治疗作用,主要表现在能明显降低肝脏重量指数,降低ALT、AST,能升高血清白蛋白(ALB),纠正白球蛋白比(A/G),显著减轻慢性肝损伤大鼠病理损伤,提示该制剂对慢性肝损伤有保护作用。降低肝组织胶原纤维含量(胶原总数目、胶原总面积),抑制胶原纤维生成,减轻肝硬化病变。     

肝乐宁粉针剂对实验性肝损伤的保护作用

研究肝乐宁粉针剂对实验性肝损伤的保护作用。方法：采用四氯化碳致小鼠和大鼠肝脏损伤,测定生化指标及观察病理组织学改变。结果：肝乐宁粉针剂能显著降低四氯化碳引起的急性肝损伤小鼠和慢性肝损伤大鼠血清丙氨酸氨基转换酶和天门冬氨酸氨基转换酶增高;亦能明显降低大鼠血清唾液酸和肝羟脯氨酸含量,升高血清总蛋白和白蛋白水平;病理组织学检查肝乐宁粉针剂明显减轻肝细胞的变性和坏死,并抑制慢性肝损伤胶原纤维形成。结论：肝乐宁粉针剂具有肝细胞保护及抗肝纤维化作用。     

黄芪胶囊对化学性肝损伤大鼠的治疗作用

目的通过黄芪胶囊对CCl4大鼠慢性肝损伤的治疗试验,评价黄芪胶囊保肝降酶的作用。方法大鼠sc 2 mL.kg-125%CCl4,每周2次,连续8周,制作大鼠慢性肝损伤模型。自给CCl4第5次后,开始ig黄芪胶囊,qd,连续5周,观察黄芪胶囊对CCl4造成大鼠慢性肝损伤的治疗作用。结果黄芪胶囊显著降低大鼠血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶,降低肝干重/湿重比值,降低肝系数,减轻肝组织病理损伤的程度,并增加肝细胞中肝糖原的含量。结论黄芪胶囊通过降低转氨酶,升高肝糖原水平,减轻肝脏损伤程度从而起到对CCl4引起大鼠肝损伤的保护作用。     

丹参注射液对大鼠脑缺血再灌注肝损伤影响的实验研究

目的研究丹参注射液对大鼠缺血再灌注肝损伤的影响。方法采用Pulsinelli方法建立大鼠急性全脑缺血再灌注模型。将Wistar大鼠随机分为3组,分别为对照组(A组)、缺血再灌注组(B组)、丹参+缺血再灌注组(C组),每组各9例。分别测定3组的血清ALT、AST、LDH的含量及肝组织超氧化物歧化酶(SOD)、丙二醛(MDA),观察肝细胞形态学变化。结果治疗组血清ALT、AST、LDH含量及肝组织MDA含量明显低于缺血再灌注组(P<0.01);肝组织SOD含量明显高于缺血再灌注组(P<0.01);肝细胞形态学变化明显减轻。结论丹参可以减轻大鼠脑缺血再灌注所致的肝脏损伤,对肝细胞有一定的保护作用。     

肝细胞生长因子合用丹参抗肝纤维化的疗效观察

目的：研究肝细胞生长因子（HGF）合用丹参与各自单用治疗慢性乙型肝炎（CHB）对肝纤维化的影响。方法：140例患分为肝细胞生长因子合用丹参组，肝细胞生长因子组，丹参组及对照组。比较四组治疗前后的血清透明质酸（HA），层粘蛋白（LN），Ⅲ型前胶原（PCⅢ），Ⅳ型胶原（Ⅳ－C）等肝纤维化指标的变化。结果：治疗后各组肝纤维化指标均较治疗前有不同程度改善，联合治疗组HA与治疗前及对照组，HGF组治疗后相比P＜0．01，与丹参组治疗相比P＜0．05；LN与治疗前及对照组，丹参组治疗后比P＜0．01；Ⅳ－C与治疗前比P＜0．01，与对照组，HGF组治疗后比P＜0．05；PCⅢ与治疗前，对照组治疗后比P＜0．01。结论：肝细胞生长因子合用丹参对慢性乙肝的抗肝纤维化的作用，效果优于单用HGF或丹参（P＜0．05或0．01），以HA的改善最为显。     

三七丹参对实验性肝纤维化的影响

目的：探讨不同剂量三七丹参（Sanqidanshen Tablet）对四氯化碳（CCl4）所致实验性肝纤维化的防治作用及量效关系。方法：采用CCl4复制小鼠肝纤维化模型,同时用0．5g/kg、1g/kg和2g/kg的三七丹参治疗,测定血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、白蛋白（ALB）、透明质酸（HA）,Ⅲ型前胶原（PCⅢ）,Ⅳ型胶原（Ⅳ—C）,层粘蛋白（LN）,并以光镜观察肝脏组织学改变,进行炎症活动度分级及肝纤维化分期。综合分析不同剂量三七丹参对CCl4中毒性肝纤维化的防治作用。结果：高、中、低剂量三七丹参均有降低ALT、AST的作用。并显著降低HA、PCⅢ和ⅣC。经治疗后的肝细胞变性、坏死及纤维组织增生明显减少。其中高、中剂量组的疗效比低剂量组好,而高、中剂量组两者之间的差异无显著性。结论：表明三七丹参具有抗实验性肝纤维化的作用,三七丹参高、中剂量组防治肝纤维化的作用优于低剂量组。     

肝细胞程序性坏死在肝损伤中的研究进展

各种致病因子损伤肝脏时会导致肝细胞死亡。持续的肝细胞死亡将诱发并加重慢性炎症与纤维化,最终引起肝硬化,甚至肝癌。因此,控制肝细胞死亡是改善肝损伤的有效策略。程序性坏死(necroptosis)是指一种受信号分子调控,具有典型坏死样形态的新的细胞死亡形式。现已证实,细胞程序性坏死在药源性肝损伤、免疫性肝损伤、酒精性脂肪肝、非酒精性脂肪肝、肝纤维化等多种肝损伤中扮演着重要角色。该文就近年来肝细胞程序性坏死在肝损伤中的研究进展作一综述,旨在为肝脏疾病的病理机制与相关治疗药物的研究提供新的视角和靶标。     

Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride-induced hepatic fibrosis in rats

Carbon tetrachloride (CCl4) is metabolized by cytochrome P450 to form a reactive trichloromethyl radical that triggers a chain of lipid peroxidation. These changes lead to cell injury, and chronic liver injury leads to excessive deposition of collagen in liver, resulting in liver fibrosis. The aim of this study was to evaluate the effects of long-term Salvia miltiorrhiza administration in CCl4-induced hepatic injury in rats. Salvia miltiorrhiza (10, 25 or 50 mg kg(-1) twice a day) was given for 9 weeks, beginning at the same time as the injections of CCl4. Rats receiving CCl4 alone showed a decreased hepatic glutathione level and an increased glutathione-S-transferase content. The hepatic thiobarbituratic acid-reactive substance levels were increased. CCl4 also caused a prominent collagen deposition in liver histology that was further supported by the increased hepatic mRNA expression of transforming growth factor-beta1, tissue inhibitor of metalloproteinase-1 and procollagen I. Salvia miltiorrhiza administration led to a dose-dependent increase in hepatic glutathione levels and a decrease in peroxidation products. Additionally, it reduced the mRNA expression of markers for hepatic fibrogenesis. In conclusion, long-term administration of Salvia miltiorrhiza in rats ameliorated the CCl4-induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis.     

路路通胶囊的质量标准

目的:建立路路通胶囊的质量控制方法.方法:用薄层色谱法对三七、赤芍、当归、丹参进行定性鉴别;高效液相色谱法测定路路通胶囊中阿魏酸的含量,采用Diamonsil C18柱(250 mm×4.6 mm,5 μm),以甲醇-0.1%磷酸溶液(30:70)为流动相;流速为1.0 ml·min-1;柱温:25℃;检测波长为320 nm.结果:TLC法检出了三七、赤芍、当归、丹参特征斑点,阿魏酸进样量在0.010～0.103 μg范围内线性关系良好,r=1.000 0,平均加样回收率为99.77%,RSD为0.93%(n＝9).结论:所建立的方法简便、稳定、准确、重复性好,可作为本品的质量控制方法.     

壳聚糖加首乌、丹参和牛膝对实验性脂肪肝大鼠的保护作用

目的 :观察壳聚糖加中药首乌、丹参和牛膝对实验性脂肪肝大鼠的预防作用。方法 :在小剂量四氯化碳致肝损伤的基础上 ,合并应用高脂饮食复制大鼠脂肪肝模型 ,同时分别给予不同浓度的药物 ,以肝脏的脂质含量为衡量标准 ,并应用计算机彩色图象分析技术测量脂肪变性 (脂变 )面积 ,观察药物预防效果。结果 :四氯化碳损伤肝脏合并高脂饮食可引起大鼠肝脏明显的脂变 ,表现为肝组织三酰甘油 (TG)、总胆固醇 (TC)含量显著增加 ,SOD活性明显降低 ,病理切片检查显示肝细胞肿胀 ,内部充满大小不等的脂滴 ,而药物防治组大鼠与模型组相比肝组织TG和TC值显著降低 ,肝细胞的脂变程度明显小于模型组 ,表现为脂滴减少 ,脂变面积缩小 ,SOD活性逐渐升高并恢复正常 ,其改善程度随用药剂量的增加而增加。结论 :该药物对脂肪肝的形成具有明显的预防作用。     

Protective mechanism of salvia miltiorrhiza on carbon tetrachloride-induced acute hepatotoxicity in rats

The purpose of this study was to investigate the possible mechanisms of Salvia miltiorrhiza (Sm) in carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. Male Wistar rats received a single dose of CCl(4) (2 ml/kg in corn oil, intraperitoneally). Three hours after CCl(4) intoxication, rats received either Sm (100 mg/kg) or silymarin (100 mg/kg) by gastrogavage twice a day for 2 consecutive days. CCl(4)-induced liver damage was shown by significant elevation of serum aminotransferase levels. Additionally, a significant decrease was observed in hepatic microsomal P450 2E1 protein content and hepatic concentrations of antioxidant enzymes. In contrast, rats given both Sm and silymarin supplement had less elevation of serum aminotransferase concentrations associated with less severe lobular damage of hepatocytes than rats receiving CCl(4) alone. Sm administration restored the reduction of hepatic microsomal P450 2E1 protein content as well as inducing an increase in hepatic glutathione concentration. On the other hand, administration of silymarin resulted in an elevation of hepatic superoxide dismutase levels. Moreover, both Sm and silymarin treatment inhibited the elevation of hepatic inducible nitric oxide (iNOS) protein content and nitrite concentration in liver homogenate 24 h after CCl(4) intoxication. We concluded that administration of Sm is effective in amelioration of CCl(4)-induced hepatotoxicity. This effect may be due to its ability to decrease the metabolic activation of CCl(4) by an increase in P450 2E1 protein content and its antioxidant activity associated with less increase in hepatic iNOS protein content.     

薄层色谱法鉴别糖尿灵片中丹参和三七

目的探讨糖尿灵片中丹参和三七的鉴别方法。方法采用薄层色谱法。结果薄层色谱斑点清晰,相互间分离良好,空白实验表明阴性样品对药材的鉴别没有干扰。结论方法简使快速,可用于本制剂的质量控制。     

Water-soluble extract of Salvia miltiorrhiza ameliorates carbon tetrachloride-mediated hepatic apoptosis in rats

Apoptosis is one of the events that are involved in liver fibrogenesis. Thus, factors that affect apoptosis may be used to modulate liver fibrosis. We have recently reported that Salvia miltiorrhiza plays a protective role in carbon tetrachloride (CCl4)-induced hepatic fibrosis. In this study, we aimed to evaluate whether S. miltiorrhiza modulated CCl4-induced hepatic apoptosis in rats. Male Wistar rats were given orally either vehicle or water-extract of S. miltiorrhiza (50 mg kg(-1) twice daily) for nine weeks beginning from the start of CCl4 administration. A group of normal rats was included for comparison. Hepatocyte DNA fragmentation and cytosolic caspase-3 and caspase-8 activity were determined in the experimental animals. Hepatic cytosolic Bax, Bcl-2, cytochrome c, and calpain-mu expressions were measured by Western blot analysis. Hepatic mitochondrial glutathione levels were assessed by colorimetric assay. Compared with normal rats, rats receiving CCl4 alone showed profound DNA fragmentation associated with an increased cytosolic fraction of cytochrome c and calpain-mu protein expressions and a decreased mitochondrial glutathione level. In contrast, a decreased laddering of DNA fragmentation was noted in rats receiving CCl4 plus S. miltiorrhiza extract. The mitochondrial glutathione level was significantly increased in rats receiving CCl4 plus S. miltiorrhiza extract compared with those receiving CCl4 alone. Additionally, cytosolic caspase-3 activity and cytosolic fractions of Bax, Bcl-2, cytochrome c, and calpain-mu protein expressions were decreased in rats receiving CCl4 plus S. miltiorrhiza extract compared with those receiving CCl4 alone. The cytosolic caspase-8 activity in rats receiving CCl4 alone was no different from those receiving CCl4 plus S. miltiorrhiza extract. These results indicated that chronic administration of S. miltiorrhiza ameliorated CCl4-mediatd hepatic apoptosis in rats. This effect may be related to the antioxidant properties of S. miltiorrhiza.     

Effects of salvianolic acid a on oxidative stress and liver injury induced by carbon tetrachloride in rats

In the present study, we investigated the hepatoprotective effects of salvianolic acid A, a novel antioxidant, against oxidative stress and acute liver injury induced by carbon tetrachloride (CCl(4)) in rats, and the mechanisms underlying its protective effects. Administration of CCl(4) to rats caused severe hepatic damage, as demonstrated by the significant increase in the levels of serum alanine aminotransferase, aspartate aminotransferase and classic histological changes including hepatocyte necrosis or apoptosis, haemorrhage, fatty degeneration, etc. Co-treatment with salvianolic acid A (20 mg/kg, intraperitoneally), a water-soluble extract from a Chinese traditional drug, Radix Salvia miltiorrhiza, significantly decreased CCl(4)-induced hepatotoxicity. Salvianolic acid A not only decreased serum alanine aminotransferase, aspartate aminotransferas levels and ameliorated histopathological manifestations in CCl(4)-treated rats, but also reduced oxidative stress, as evidenced by decreased reactive oxygen species production and malondialdehyde concentrations in the liver tissues, combined with elevated hepatic superoxide dismutase activity and gluthathione content. In addition, salvianolic acid A treatment remarkably reduced intrahepatic tumour necrosis factor-alpha concentrations and caspase-3 activities as compared with the CCl(4)-treated rats. The results suggested that treatment with salvianolic acid A provides a potent protective effect against acute hepatic damage caused by CCl(4) in rats, which may mainly be related to its antioxidative effect.     

丹参水提液对抗大鼠泼尼松性骨质疏松的作用研究

目的:观察中药丹参水提液对泼尼松所致的大鼠骨质疏松的对抗作用。方法:50只大鼠随机分成正常对照组、泼尼松组和丹参水提液高、中、低剂量组,每组10只。分别灌喂相应药物,每日1次,连续8周后取血清检测生化指标,对骨进行组织切片检查,长度、宽度以及骨质的测量。结果:泼尼松组大鼠股骨重量、骨羟脯氨酸和骨钙含量比正常对照组明显降低,骨髓腔中脂肪组织增多(P<0.01),血浆胆固醇含量上升、碱性磷酸酶和高密度脂蛋白含量下降(P<0.05)。丹参水提液能有效提高骨的重量和骨质的含量(P<0.05),减少骨髓腔中脂肪的含量,升高碱性磷酸酶和高密度脂蛋白含量(P<0.05),但量效关系不明显。结论:泼尼松可抑制大鼠的骨生长及引起骨丢失,丹参水提液对其有较好的对抗作用。     

BP神经网络结合遗传算法用于丹参提取工艺的多目标优化

目的:使用BP神经网络结合遗传算法用于丹参提取工艺的多目标优化。方法:通过已知文献的丹参提取工艺优化实例,采用均匀设计法优化BP神经网络模型参数,并建立网络模型,再利用遗传算法对网络进行多目标寻优,获得丹参最佳提取工艺。结果:BP神经网络结合遗传算法用于丹参提取工艺的多目标优化,模型拟合度和预测性均高于文献采用的多元回归法。结论:BP神经网络结合遗传算法可用于丹参提取工艺的多目标优化。     

Protective effect of salvianic acid a on acute liver injury induced by carbon tetrachloride in rats

Previous research has shown that salvianic acid A [2-(3,4-dihydroxyphenyl)-2-hydroxy-propanoic acid, SA] extracted from Salvia miltiorrhiza BGE (Danshen) markedly inhibits lipid peroxidation of mitochondrial membrane of hepatic cells in vitro. The present study was conducted to examine protective effect of SA on liver injury induced by carbon tetrachloride (CCl4) and its possible mechanism in vivo. Male Sprague-Dawley rats weighing 180-200 g were used in the experiments. Five mmol/kg CCl4 in olive oil was given to rats i.p. Spectrophotometrical method was used to measure activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as malondialdehyde (MDA) level in hepatic tissue and the rate of superoxide anion (O2*-) generation in hepatic submitochondrial particles. Hepatic histological structure was observed under light microscopy. CCl4 caused significant changes of activities of the enzymes, MDA level, and the rate of O2*- generation and histopathological changes of acute hepatic injury were noted. SA reversed the significant changes induced by CCl4. These results demonstrate that SA produces protective action on acute hepatic injury induced by CCl4 via an antioxidative mechanism.