岗松挥发油对实验性肝损害的防治作用

本研究表明,岗松油对四氯化碳、硫代乙酰胺、醋酸强的松龙引起的小鼠SGPT升高有明显的降低作用,使BSP潴留量减少,相应肝组织病变减轻。此外,岗松油对四氯化碳损害小鼠和正常小鼠戊巴比妥钠的睡眠时间均能明显缩短。对巴豆油引起小鼠耳部炎症有明显的抗炎作用。岗松油的毒性很低,口服半数致死量(LD_(50)为3,758±539mg/kg,给兔灌胃687～1030mg/kg每天一次,连续30天,一般表现、血象、肝肾功能及病理检查均未见明显的改变。     

二苯乙烯(芪)的一些药理作用

芪(二苯乙烯)通常用于化学工业,对其药理活性的研究很少。通过动物实验我们发现芪能明显保护CCl₄引起的小鼠肝损害,表现在使高的SGPT及SGOT降低、BSP潴留减少、肝组织病变减轻等。芪明显促进肝糖元生成,此作用强度与可的松相近,但芪没有可的松那样的抗炎作用。在去肾上腺小鼠,芪仍能明显促进肝糖元生成,故此作用似乎不通过体内的垂体-肾上腺系统。芪对小鼠戊巴比妥睡眠时间影响不明显。根据实验资料分析,芪对CCl₄肝损害的保护机制大概不是通过酶诱导,也不象某些抗氧化剂那样直接对抗CCl₄的作用,但有可能与其促进肝糖元生成有某种关系。芪有微弱的雌激素作用(约为己烯雌酚的数万分之一)。芪的毒性很低,小鼠一次腹腔注射LD₅₀为6.5 g/kg,灌胃LD₅₀大于8 g/kg,但油溶液毒性较大(灌胃LD₅₀为0.92g/kg)。长期大量给予芪,对雄小鼠的生长及睾丸发育有抑制作用,给狗服芪50 mg/kg/天连续一个月以上未见明显异常反应。     

复肝康冲剂的保肝作用

复肝康冲剂对四氯化碳所致小鼠和大鼠肝损伤致死有较好的保护作用;对四氯化碳引起小鼠SGPT升高有明显的抑制作用(P<0.01),并对四氯化碳所致小鼠损伤肝细胞有促进其修复的作用;大鼠灌胃能明显增强其免疫机能;小鼠灌胃LD50在20g/kg以上,大鼠慢性毒性实验未见毒性反应。     

盐酸关附甲素注射液对实验性心律失常的作用

关附甲素是从关白附子块根中提取的一种新生物碱。实验表明IGFAH(50　g/ml)对大鼠离体心脏结扎冠脉诱发的室性心律失常有明显的保护作用,IGFAH3、6、12mg/kgiv能显著提高电刺激麻醉兔心室致颤阈值,IGPAH13.4,16.8,21.0mg/kgiv能明显对抗Cal₂-Ach液诱发小鼠房扑(颤),其ED₂为12.4±1.5mg/kg。IGFAH10,25,40mg/kgiv对乌头碱诱发的大鼠室性心律失常有明显的保护作用。IGFAH小鼠iv的LD₅₀为163.9mg/kg,其96%可信限为151.9—176.7mg/kg。     

烟浪丁的抗心律失常作用

NICO 100 mg/kg iv,可明显对抗乌头碱和BaCl₂诱发大鼠及氯仿-肾上腺素引起兔的心律失常;降低CaCl₂所致的大鼠室颤率;提高豚鼠心脏哇巴因中毒时的耐量。50 mg/kg iv,也可预防结扎大鼠左冠状动脉引起的心律失常。50～100 mg/kg ip,能降低氯仿或ACh—CaCl₂引起的小鼠室颤率或房颤(扑)率。NICO可减慢豚鼠心率,且可拮抗异丙肾上腺素的正性变率作用。     

原代培养大鼠肝细胞中观察十种中药的抗肝毒作用

利用半乳糖胺GalN或四氯化碳CCI₄引起原代培养大鼠肝细胞损伤模型,研究10种中药水提液的抗肝毒作用。结果表明:丹参、田基黄、过路黄、野萄花2—50mg/ml;女贞子、车前子10—50mg/ml;山栀、垂盆草、海金沙及干姜50mg/ml可使含GaIN5x10^-3mol/L肝细胞培养液中GPT活性显著降低。其中丹参与田基黄又分别在CCI₄1.0x10^-2mol/L损伤肝细胞培养液及CGI₄实验性肝损伤小鼠中验证,均显示明显的护肝作用.     

当归多糖对不同化学性肝损伤的干预作用

目的观察纯化当归多糖对酒精性及四氯化碳性肝损伤的干预作用,并探讨其初步机制。方法分别采用乙醇及四氯化碳制造小鼠肝损伤模型,给予纯化当归多糖,按100mg/kg和200mg/kg口服给药进行干预。观察血清sALT、sAST的变化;测定抗氧化指标SOD、MDA、GSH的含量;以苯胺羟化酶反映CYP2E1活性。结果当归多糖两剂量组均可降低酒精性及四氯化碳性肝损伤模型组的sALT、sAST,减轻肝脏损伤;两组引起的抗氧化功能下降均可被当归多糖不同程度的抑制;当归多糖可抑制乙醇所致的CYP2E1上调,但对四氯化碳所致的CYP2E1酶活性降低却无明显影响。大剂量组的上述作用更为明显。结论纯化当归多糖对不同化学性肝损伤均有明显的干预作用,但其干预能力因保护机制不同而有所差别。     

利血平与优降宁对动物痛阈和吗啡镇痛作用影响因素探讨

采用三种测痛方法,观察了利血平、优降宁对小鼠、大鼠正常痛阈和吗啡镇痛作用的影响,结果表明:ip利血平2 mg/kg,优降宁100 mg/kg均能明显抑制小鼠扭体反应;ip利血平1 mg/kg能明显提高小鼠热板反应时间,但ip优降宁75 mg/kg无明显影响;ip利血平6 mg/kg,优降宁75 mg/kg对大鼠甩尾反应时间均无明显影响;利血平(小鼠0.5～1.0 mg/kg,大鼠2 mg/kg ip)能明显对抗吗啡镇痛作用;优降宁(小鼠35 mg/kg,大鼠50 mg/kg ip)能明显增强吗啡镇痛作用,并能“逆转”利血平对抗吗啡镇痛作用。其“逆转”作用的强弱取决于利血平、优降宁给药的先后次序。     

利血平与优降宁对动物痛阈和吗啡镇痛作用影响因素探讨

采用三种测痛方法,观察了利血平、优降宁对小鼠、大鼠正常痛阈和吗啡镇痛作用的影响,结果表明:ip利血平2 mg/kg,优降宁100 mg/kg均能明显抑制小鼠扭体反应;ip利血平1 mg/kg能明显提高小鼠热板反应时间,但ip优降宁75 mg/kg无明显影响;ip利血平6 mg/kg,优降宁75 mg/kg对大鼠甩尾反应时间均无明显影响;利血平(小鼠0.5～1.0 mg/kg,大鼠2 mg/kg ip)能明显对抗吗啡镇痛作用;优降宁(小鼠35 mg/kg,大鼠50 mg/kg ip)能明显增强吗啡镇痛作用,并能“逆转”利血平对抗吗啡镇痛作用。其“逆转”作用的强弱取决于利血平、优降宁给药的先后次序。     

抗癌新药-乙双吗啉(AT-1727)的药理研究

乙双吗啉(AT-1727)是我国合成的一种抗癌新药。它是一种双内酰亚胺化合物,实验证明,乙双吗啉对小鼠肉瘤S₃₇、S₁₈₀有显著抗肿瘤作用,对ECS,HCS,脑瘤B₂₂及L₆₁₅等移植性肿瘤亦有明显抗肿瘤作用。它对S₃₇的50%抑制剂量(ID₅₀)为1.88 mg/kg(ip)及6.61 mg/kg(po)。其抗肿瘤作用与给药方案有一定关系。乙双吗啉对小白鼠毒性LD₅₀为372.8±27.mg/kg(ip)及243.8±26.1 mg/kg(po)。因此,乙双吗啉腹腔注射及口服时,对S₃₇的化疗指数分别为47.5及36.9。给健康犬肌肉注射乙双吗啉25及50 mg/kg/天,连用10天,除出现食量减少,白细胞轻度下降外,对红细胞,血小板、肝、肾功能均无明显影响。乙双吗啉对以溶血素反应为指标的体液免疫有抑制作用;对以移植物抗宿主反应为指标的细胞免疫则无抑制作用。     

联苯双酯、二苯乙烯、五仁醇及灵芝对小鼠实验性肝损伤保护作用的比较

联苯双酯系合成五味子丙素的一种中间产物。二苯乙烯系合成五味子丙素所用的一种化工原料,我们对这两种化合物与五味子和灵芝对小鼠肝脏的作用进行了比较,结果表明,对于四氯化碳、硫代乙酰胺引起的血清谷丙转氨酶(SGPT)升高,联苯双酯、五味子、灵芝及二苯乙烯均有降低作用。对强的松龙所致的SGPT升高,仅联苯双酯有降低作用,其余三种无效。对于四氯化碳和硫代乙酰胺引起的小鼠肝脏甘油三酯的蓄积,除联苯双酯无效外,五味子、灵芝及二苯乙烯均有明显降低作用。对强的松龙引起小鼠肝脏甘油三酯的蓄积,仅二苯乙烯能使其降低,而灵芝使其蓄积更多,联苯双酯和五味子则无明显影响,对DL-乙硫氨酸引起的脂肪肝,灵芝和二苯乙烯有明显预防作用,五味子无效,联苯双酯使蓄积更明显。此外,五味子和二苯乙烯能促进小鼠肝糖原的生成,联苯双酯对四氯化碳中毒小鼠有缩短戊巴比妥钠睡眠的作用。总之,上述四种药物对小鼠肝脏的作用,有的相似,有的不同。从临床治疗角度考虑,试用药物时,合并用药可能更好,这样各药可以取长补短。     

Protective effects of seabuckthorn (Hippophae rhamnoides L.) seed oil against carbon tetrachloride-induced hepatotoxicity in mice

The present study examined the protective effects of seabuckthorn (Hippophae rhamnoides L., SBT) seed oil on carbon tetrachloride (CCl₄)-induced hepatic damage in male ICR mice. Our results showed that oral administration of SBT seed oil at doses of 0.26, 1.30, and 2.60 mg/kg for 8 weeks significantly reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), and cholesterol at least 13% in serum, and the level of malondialdehyde (MDA) in liver at least 22%, that was induced by CCl₄ (1 mL/kg) in mice. Moreover, the treatment of SBT seed oil was also found to significantly increase the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), and GSH content in liver up to 134%. Our study found that the optimal dose of SBT seed oil was 0.26 mg/kg, as the minimum amount exhibiting the greatest hepatoprotective effects on CCl₄-induced liver injury. Overall, the hepatoprotective effect of SBT seed oil at all tested doses was found to be comparable to that of silymarin (200 mg/kg) and have been supported by the evaluation of the liver histopathology in mice.     

Comparison of TGF-β, PDGF,and CTGF in hepatic fibrosis models using DMN,CCl4, and TAA

Three chemotoxins including dimethylnitrosamine (DMN), carbon tetrachloride (CCl₄), and thioacetamide (TAA) are commonly used in hepatofibrotic models. We aimed to draw characteristics of histopathology and pro-fibrogenic cytokines including TGF-β, PDGF and CTGF among three models. Rats were divided into six groups and intra-peritoneally injected with DMN (10?mg/kg, for three weeks, three consecutive days weekly), CCl₄ (1.6?g/kg, for 10 weeks, twice weekly), TAA (200?mg/kg, for 12 weeks, twice weekly) or their corresponded treatment for each control group. The liver weights were decreased in DMN model, but not other models. Ascites were occurred as 3-, 2-, and 7-rats in DMN, CCl₄, and TAA model, respectively. The lipid peroxidation was highest in CCl₄ model, serum levels of liver enzymes were increased as similar severity. The hepatofibrotic alterations were remarkable in DMN and TAA model, but not CCl₄ as evidenced by the Masson trichrome staining and hydroxyproline. The immunohistochemistry for α-SAM showed that the DMN model was most severely enhanced than other models. On the other hand, hepatic tissue levels of pro-fibrogenic cytokines including TGF-β, PDGF, and CTGF were generally increased in three models, but totally different among models or measurement resources. Especially, serum levels of three cytokines were remarkably increased by CCl₄ injection and CTGF levels in both hepatic tissue and serum were highest in CCl₄ group. Our results firstly demonstrated comparative study for features of morphological finding and pro-fibrogenic cytokines in serum and hepatic protein levels among three models. Above results would be a helpful reference for hepatofibrotic studies.     

锌二氢卟吩e4的合成及初步抗胃溃疡活性和对急性肝损伤的保护作用

目的　研究锌二氢卟吩e₄(1)的合成及实验性抗溃疡活性和对急性肝损伤的保护作用。方法　蚕沙叶绿素粗品经酸碱降解反应制得二氢卟吩e₆(3),3经吡啶回流降解制得二氢卟吩e₄(2),2与醋酸锌络合制得1;并测定1对消炎痛诱发的大鼠胃溃疡的保护作用及对硫代乙酰胺、四氯化碳所致小鼠急性肝损伤的防治作用。结果　1为新化合物。生物活性实验结果表明,1能显著降低消炎痛诱发的大鼠胃溃疡指数和溃疡个数;能显著降低小鼠硫代乙酰胺或四氯化碳急性肝损伤后升高的SGPT活性。结论　1对消炎痛诱发的大鼠胃溃疡和硫代乙酰胺、四氯化碳所致小鼠急性肝损伤具有显著的保护作用。     

Resveratrol ameliorates carbon tetrachloride-induced acute liver injury in mice

Present investigation aimed to evaluate the hepatoprotective potential of resveratrol (30 mg/kg, po) in mice following two different routes (po and sc) of exposure to carbon tetrachloride (CCl₄, 1.0 ml/kg). Administration of CCl₄ caused significant increase in the release of transaminases, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transpeptidase, creatinine kinase, total bilirubin, urea and uric acid in serum. Significantly enhanced hepatic lipid peroxidation and oxidized glutathione with marked depletion in reduced glutathione were observed after CCl₄ intoxication. It was also found that CCl₄ administration caused severe alterations in liver histology. Hepatic injury was more severe in those animals who received CCl₄ by oral route than those who exposed to CCl₄ subcutaneously. Resveratrol treatment was able to mitigate hepatic damage induced by acute intoxication of CCl₄ and showed pronounced curative effect against lipid peroxidation and deviated serum enzymatic variables as well as maintained glutathione status toward control. Treatment of resveratrol lessened CCl₄ induced damage in liver. The results of the present study suggest that resveratrol has potential to exert curative effects against liver injury.     

Prevention of Carbon Tetrachloride-Induced Hepatotoxicity by the Ethanol Extract of Capparis moonii Fruits in Rats

The effect of the ethanol extract of Capparis moonii Hook. f. Thoms. (Capparidaceae) fruits was studied in carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. The hepatotoxicity was induced in rats with the administration of 1 : 1 (v/v) mixture of CCl₄ in olive oil at the dose of 1 ml/kg subcutaneously on day 7. The ethanol extract of C. moonii (200 mg/kg) and the standard drug silymarin (25 mg/kg) were given orally from day 1 to day 9. The extract of C. moonii produced significant (p &lt; 0.001) lowering of the elevated Serum glutamic oxaloacetic transaminace (SGOT) Serum glutamicpyraric transaminase (SGPT), alkaline phosphatase (ALP), and a rise of depleted total protein when compared with the toxic control. The results were comparable with the standard drug silymarin.     

Rossicaside B Protects against Carbon Tetrachloride‐induced Hepatotoxicity in Mice

Abstract: The protective effect of rossicaside B, the major phenylpropanoid glycoside from Boschniakia rossica, on CCl₄‐induced hepatotoxicity and the mechanisms underlying its protective effect were investigated. The mice were administered orally with rossicaside B (100 or 200 mg/kg of body weight) 48, 24 and 1 hr before CCl₄ (0.5 ml/kg of body weight) administration. The CCl₄ challenge caused a marked increase in the levels of serum aspartate aminotransferase, alanine aminotransferase and of tumour necrosis factor‐α, and propagated lipid peroxidation with a concomitant reduction in reduced glutathione (GSH) and antioxidative enzyme activities in the liver. The administration of rossicaside B to CCl₄‐treated mice not only decreased the serum toxicity marker enzymes and TNF‐α but also reduced hepatic oxidative stress, as demonstrated by decreased lipid hydroperoxide and thiobarbituric acid‐reactive substance concentrations, combined with elevated GSH content and antioxidative enzyme activities in the liver tissues. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2) and haem oxygenase‐1 (HO‐1) were elevated after CCl₄ treatment while the cytochrome P450 2E1 (CYP2E1)‐specific monooxygenase activity was suppressed. Rossicaside B treatment inhibited the formation of liver nitrite, reduced the over‐expression of iNOS and COX‐2 proteins, but increased the CYP2E1 function compared with the CCl₄‐treated mice. However, the protein expression of HO‐1 was further elevated by rossicaside B treatment. The results demonstrate that rossicaside B provides a protective action on CCl₄‐induced acute hepatic injury, which may be related to its antioxidative activity, suppressed inflammatory responses, induced HO‐1 expression and improved CYP2E1 function in the liver.     

Protective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat

Summary The effects of saikosaponin-d extracted from the roots of Bupleurum falcatum L. on carbon tetrachloride-induced hepatic injury were studied in rats. Pretreatment with saikosaponin-d produced a remarkable inhibitory action on acute hepatic injury by CCl₄. A significant inhibition of lipid peroxidation induced by an acute dose of CCl₄ in the liver of rats pre-treated with saikosaponin-d was also noted.Continuous injection of CCl₄ caused liver cirrhosis in rats but the severity of cirrhosis was reduced in rats treated simultaneously with CCl₄ and saikosaponin-d.     

乌苏酸对实验性肝损伤的防治作用

实验表明乌苏酸能使急性肝损伤大鼠SGPT及肝甘油三脂下降,血清甘油三脂、β脂蛋白及肝糖原含量增加,并能减轻肝细胞变性、坏死。推测乌苏酸为陆英抗肝损伤的主要成分。