抗痹颗粒对糖尿病周围神经病变大鼠的疗效和氧化应激的影响

目的 探讨抗痹颗粒对糖尿病周围神经病变（DPN）大鼠的疗效和氧化应激指标的影响。方法 取SD大鼠喂食高能饲料结合腹腔注射链脲佐菌素（STZ）制备DPN大鼠模型。模型大鼠随机分为3组：模型组、抗痹颗粒高剂量组[3.24 g/（kg·d）]、抗痹颗粒低剂量组[0.81 g/（kg·d）],每组10只。另取10只作为正常组。正常组和模型组给予生理盐水灌胃,抗痹颗粒给药组按剂量灌胃给药,1次/d,连续给药8周,实验总计9周。在实验的0、1、5、9周测量大鼠的体质量、血糖水平。在实验第9周,处死大鼠,切取部分坐骨神经组织测超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）、过氧化氢酶（CAT）活性水平。结果 与正常组相比,模型组体质量、血糖明显增加（P <0.05）,SOD、CAT活性明显降低,MDA含量升高,GSH含量降低;与模型组相比,给药组体质量、血糖明显降低（P <0.01）,SOD、CAT活性明显升高,MDA含量减少,GSH含量升高。结论抗痹颗粒能够降低糖尿病周围神经病变大鼠的氧化应激反应。     

舒胆通颗粒对实验动物胆汁分泌及胆囊平滑肌的影响

目的观察舒胆通（SDT）颗粒对大鼠胆汁分泌及胆囊平滑肌的影响。方法采用在体胆汁引流法,观察单次给予SDT对大鼠胆汁分泌以及总胆红素（TB）的影响;采用离体试验法观察SDT对豚鼠胆囊平滑肌条的直接作用及其对阿托品、酚妥拉明、苯海拉明、雷尼替丁的拮抗作用。结果SDT 5,10,20 g.kg^-1剂量能使大鼠给药后30－90 min时段胆汁分泌增加,但胆汁中TB水平无明显改变;终浓度为2.5×10^-4,5×10^-4,1×10^-3 mg.mL^-1的SDT能使离体豚鼠胆囊肌条张力增高、收缩频率加快、收缩幅度增加,并呈现明显的量效关系,其兴奋作用可被阿托品完全阻断,也可被酚妥拉明部分阻断,但不能被苯海拉明、雷尼替丁所阻断。结论SDT能增强胆囊平滑肌的兴奋性,促进胆汁分泌;其利胆作用可能主要经由胆碱能M受体介导,部分经由肾上腺素能α受体介导、而与组胺H1受体、前列腺素受体等途径无关。     

国产注射用特立帕肽的过敏性及免疫原性研究

目的 考察国产注射用特立帕肽在动物中的过敏性及免疫原性.方法 对豚鼠和家兔分别于0d和14 d注射一定浓度的特立帕肽,观察豚鼠全身变态反应及对家兔的免疫原性,并采用ELISA分析家兔血清抗体的变化规律.结果 给药后豚鼠未见明显全身变态反应.家兔免疫原性实验结果表明,低剂量组（1 μg/kg）血清中的IgE含量经免疫后无明显上升;中剂量组（5μg/kg）和高剂量组（10 μg/kg）血清中IgE含量在首次免疫后略有快速上升,但随后中剂量组恢复正常,而高剂量组在加强免疫后IgE含量仍有一定上升.结论 国产注射用特立帕肽在拟定的人用剂量范围内具有很好的安全性,可供皮下注射给药.     

活血通腑优化方对实验性肠粘连大鼠的保护作用

目的：观察活血通腑优化方对实验性肠粘连的防治效果。通过对大鼠血清IL-6、IL-1β、TNF-α及腹腔液中转化生长因子-β1和结缔组织生长因子的蛋白含量的检测,探讨其对肠粘连防治作用的机理。方法：SD大鼠随机分为6组：正常组、模型组、四磨汤组,活血通腑优化方低、中、高剂量组;每组10只。除正常对照组外,其余各组大鼠均制备肠粘连模型。正常组和模型组灌胃生理盐水。活血通腑优化方低、中、高剂量组在造模后,灌胃给予活血通腑优化方（0.65、1.3、2.6 g/100 g）,连续给药10 d。四磨汤组灌服1 mL/100 g的四磨汤,连续给药10 d。各组大鼠于术后第11 d麻醉取下腔静脉血,ELISA法测定血清IL-6、IL-1β和TNF-α含量;并取腹腔液检测TGF-β₁和CTGF的含量,同时记录大鼠肠粘连级别。结果：与正常组相比,模型组血清IL-1β和TNF-α含量增高（P<0.01）,腹腔液中TGF-β₁和CTGF的含量也升高（P<0.01）。与模型组相比,活血通腑优化方低、中、高剂量组的肠粘连程度明显减轻（P<0.05）,血清IL-1β和TNF-α含量明显降低（P<0.05）,腹腔液中TGF-β₁和CTGF的含量明显下降（P<0.05）。结论：活血通腑优化方可剂量依赖的减轻肠粘连的程度,对肠粘连具有防治作用。其作用可能是通过下调炎性因子TNF-α、IL-1β的表达,同时与抑制TGF-β₁信号通路有关。     

防风通圣颗粒解热、抗炎、镇痛、抗病毒药效学研究

目的 研究防风通圣颗粒的解热、抗炎、镇痛、抗病毒药效作用。方法 观察防风通圣颗粒不同剂量对内毒素(脂多糖)致家兔发热的解热作用,对小鼠的镇痛作用,对二甲苯致小鼠耳廓肿胀的抗炎作用,对豚鼠气管平滑肌的舒张作用,体内抑菌作用及体内抗病毒药效作用。结果防风通圣颗粒1.6 g/kg、0.8 g/kg对内毒素(脂多糖)致家兔发热有明显降温作用,降温作用最强的时间为给药后3 h;防风通圣颗粒5.0 g/kg对冰醋酸引起的小鼠腹痛具有明显的镇痛作用(P<0.01);防风通圣颗粒5.0 g/kg、2.5 g/kg对二甲苯所致小鼠耳廓肿胀急性炎症具有明显的抑制作用(P<0.05);防风通圣颗粒3.23×10^-2g/ml、1.61×10^-2g/ml对磷酸组胺引起豚鼠离体气管平滑肌收缩均具有明显的拮抗作用,且呈一定的量效关系;防风通圣颗粒5.0 g/kg可降低金黄色葡萄球菌感染小鼠死亡率;采用呼吸道合胞病毒(RSV)-小鼠肺炎模型,以利巴韦林和双黄连作为对照药物,防风通圣颗粒组具有显著改善肺组织外观的效果,能明显降低肺组织病毒分离阳性率,对RSV感染导...     

复方金降脂胶囊急性毒性实验研究

目的 观察用金降脂给小鼠一次性灌胃引起的快速而剧烈的中毒反应。方法 50只小鼠等分5组。正常组：用蒸馏水0.8ml灌胃。纤维素组：用1%羧甲基纤维素钠（CMC-Na）0.8ml灌胃。低剂量组：按0.4ml/10g浓度为150mg/ml(6g/kg）金降脂灌胃。中剂量组：按0.4ml/10g浓度为200mg/ml(8g/kg）金降脂灌胃。高剂量组：按0.4ml/10g浓度为250mg/ml（10g/kg）金降脂灌胃。灌胃后连续观察一周。结果 一周实验期间各组均无异常、无死亡；体重增长速度正常，各组无明显差异。结论 金降脂灌胃小鼠，给予最大容积0.8ml/20g，最大剂量10g/kg（相当成人用量800倍）；无异常反应，无一死亡，足以说明金降脂是一种安全、无毒治疗剂量范围大的可靠新药。     

辣椒素对高脂血症豚鼠肝脏胆固醇和甘油三脂的影响

目的探讨辣椒素对实验性高脂血症豚鼠肝脏胆固醇(TC)和甘油三脂(TG)的影响。方法 48只豚鼠随机分为正常对照组、模型组、辣椒素高剂量组(10 mg/kg)、中剂量(5 mg/kg组)、低剂量组(2.5 mg/kg)、辛伐他汀组(1.5 mg/kg)。除正常对照组给药予普通饲料外,其余各组给予高脂饲料,造模同时给药,正常对照组每日灌胃给予等体积的生理盐水,其余灌胃给予相应剂量的药物,1次/d,共14周。实验14周末,处死动物,取肝脏检测其中TC、TG含量。结果模型组豚鼠肝脏TC、TG含量均高于正常对照组(P<0.01),给予辣椒素后,豚鼠肝脏TC、TG含量均有不同程度下降,明显低与模型组(P<0.05或0.01)。结论辣椒素能显著降低实验性高脂血症豚鼠肝脏TC、TG含量,对肝脏有保护作用。     

健脾消胀片对大鼠胆汁分泌的影响

目的：观察健脾消胀片对大鼠胆汁分泌的影响。方法：大鼠60只,分为6组,分别灌服健脾消胀片（大、中、小剂量）混悬液;舒胆通混悬液;清肝利胆胶囊混悬液和同体积的0.5%羧甲基纤维素;每天给药1次,连续给药5 d。收集各组大鼠胆汁量,检测胆汁中总胆汁酸、总胆固醇、总胆红素等含量。结果：健脾消胀片可使大鼠胆汁中胆汁酸、胆红素含量显著升高（P〈0.01）,胆固醇含量显著降低（P〈0.01）。结论：健脾消胀片有促进胆汁分泌的作用。     

加味四逆散对卡介苗加脂多糖所致小鼠肝损伤的保护作用

目的观察加味四逆散对卡介苗（BCG）＋脂多糖（LPS）所致的免疫性肝损伤小鼠的保护作用。方法60只NIH小鼠,随机分为正常组、模型组、联苯双酯组、加味四逆散大、中、小剂量组。除正常组外,其他组以BCG＋LPS方法造模,诱导小鼠免疫性肝损伤。正常组及模型组均以生理盐水0.2ml/只/次/日灌胃,联苯双酯组按150mg/kg灌胃;加味四逆散大、中、小剂量组分别按40g/kg,20g/kg,10g/kg灌胃,1次/d,连续10d。实验结束时眼球采血,分离血清检测IL-6,TNF-α。结果加味四逆散大、中剂量组血清IFN-γ、TNF-α含量明显低于模型组,差异有显著性（P〈0.01,P〈0.05）。结论大、中剂量加味四逆散对BCG＋LPS所致小鼠肝损伤具有较好的保护作用。其机制与其降低IL-6,TNF-α等炎症介质含量密切相关。     

益可颗粒对正常及糖尿病模型小鼠的降糖作用研究

目的:观察益可颗粒对正常和实验性高血糖小鼠血糖水平的影响。方法:正常小鼠连续灌胃给药15d后,利用血糖试纸检测不同剂量益可颗粒对正常小鼠血糖影响;腹腔注射四氧嘧啶制备糖尿病小鼠模型,实验随机分为7组,每组10只小鼠,即正常对照组、模型对照组,阳性对照组、联合用药组、益可颗粒高剂量组(6.0g/kg)、益可颗粒中剂量组(3.0g/kg)及益可颗粒低剂量组(1.0g/kg),连续灌胃30d后,以血搪试纸测定小鼠空腹血糖。结果:三个剂量的益可颗粒连续灌胃给药15天,均不影响正常小鼠的血糖和体重;6.0g/kg益可颗粒组连续灌胃给药30d,可明显降低四氧嘧啶诱发的高血糖小鼠血搪。结论:益可颗粒不降低正常小鼠血糖,可降低实验性糖尿病小鼠的血糖。     

复方金钱草颗粒利胆及体外抗豚鼠胆囊平滑肌痉挛作用研究

目的探讨复方金钱草颗粒利胆作用及对胆囊平滑肌痉挛的影响。方法利用胆管引流法测定给复方金钱草颗粒前后大鼠胆汁的流量及成分;通过对豚鼠胆囊肌条的观察,探讨复方金钱草颗粒对乙酰胆碱所致胆囊平滑肌痉挛的影响。结果复方金钱草颗粒7．4g／kg剂量组可显著提高大鼠的胆汁流量,显著提高胆汁中胆红素浓度;62g／L剂量组可显著抑制由乙酰胆碱引起的豚鼠胆囊痉挛。结论复方金钱草颗粒具有利胆作用,可缓解乙酰胆碱引起的胆囊痉挛。     

Glutamic acid and sodium levels in the nucleus arcuatus of the hypothalamus of adult and infant guinea pigs after oral monosodium glutamate

Monosodium glutamate (MSG) administered orally at 4 g/kg body weight (b.wt.) as a 20% solution (w/v) to 55–60-day-old guinea pigs and at 2 g/kg b.wt. as a 20% solution (w/v) to 3-day-old guinea pigs did not increase glutamie acid (GA) or sodium levels in the nucleus arcuatus of the hypothalamus (NAH) or in the thalamus lateralis (TL). Sodium chloride given by gavage at doses of sodium equimolar to MSG resulted in an increase of sodium content only in the NAH of infant guinea pigs.     

补骨脂对大鼠胆汁分泌和豚鼠胆囊平滑肌收缩力的影响

目的研究补骨脂生药粉对大鼠胆汁分泌和豚鼠胆囊平滑肌收缩力的影响。方法大鼠连续灌胃给予补骨脂生药粉（2．1g·kg-1）30天。同时设对照组。末次给药后用水合氯醛麻醉动物,进行胆总管插管。收集胆汁,比较补骨脂组与对照组在同时间点胆汁量和总胆汁量的差异。豚鼠禁食24小时后击头致毙．迅速取出胆囊．制成平滑肌条,观察不同浓度补骨脂液对平滑肌收缩力的影响。结果补骨脂2．1g·kg-1组大鼠胆汁分泌量与对照组之间无显著差异。补骨脂4．8g·L-1、2．4g·L-1、1．2g·L-1能显著增高豚鼠离体胆囊平滑肌条张力,与剂量呈现一定的正相关性。结论补骨脂对大鼠胆汁分泌没有显著影响,但是可以促进豚鼠胆囊平滑肌的收缩。     

Pharmacology of dihydroxy-dibutylether, a specific choleretic drug.

The choleretic and the general pharmacological properties of dihydroxy-dibutyl ether (Discinil) were investigated in several animal species. Discinil (DHBE) increased the bile flow in conscious rats and dogs, after both oral and i.v. administration. A choleretic effect was also observed after i.v. injection into anaesthetized rats and guinea pigs. A dose-response relationship was always obtained, the threshold dose being 25--100 mg/kg. No evidence of tachyphylaxis was observed in rats after repeated treatments. The bile hyperflow was generally accompanied by an increased excretion of the total dry residue in guinea pigs and dogs. The choleretic effect in rats was still present after pretreatment with either DL-ethionine (causing parenchymal liver damage) or atropine (blocking the cholinergic control of bile production). At low doses (25--100 mg/kg i.v.) eliciting a definite choleretic response, DHBE did not show spasmogenic and spasmolytic effects in vivo on the smooth muscles of the gallbladder of guinea pigs and dogs, neither on the stomach and intestine of mice and dogs; while it constricted the pylorus sphincter of rats. At larger doses (200--400 mg/kg i.v.) the compound showed a mild relaxing activity on Oddi's sphincter of guinea pigs and a weak spasmogenic activity either on gall bladder or on small intestine. In vitro, it caused an unspecific antagonism against the spasm induced by acetylcholine, barium chloride, histamine, 5-hydroxytryptamine and norepinephrine. In anaesthetized rats, rabbits and dogs, DHBE caused a moderate and short-lasting hypotension, and tachycardia. The threshold doses for these effects were 2--4 times superior to those being choleretic. In conscious dogs, the compound was slightly hypertensive. DHBE did not provoke important respiratory and ECG changes, neither showed diuretic nor antiphlogistic effects.     

The effect of ginseng on bile-pancreatic secretion in the rat. Increase in proteins and inhibition of total lipids and cholesterol secretion.

Ginseng is one of the most popular herbal remedies. Studies were performed in anaesthetized rats to examine the effect of ginseng on bile secretion. Male Sprague-Dawley rats were anaesthetized with intraperitoneal (i.p.) urethane (1.25 g kg(-1)) and equipped with biliary cannulas inserted into the bile duct through the sphincter of Oddi. Rats were treated with a single i.p. injection of ginseng at 25, 50 or 100 mg kg(-1) (1 ml(-1)) 30 min before bile collection; the control group received i.p. saline only at 1 ml(-1)volume. The effect of multiple doses of ginseng on bile volume and biliary composition was also studied. Ginseng was given in the higher dose of 100 mg kg(-1) (1 ml(-1), i.p.) every 12 hours for 2 days. Bile was collected in 15 min fractions for 90 min. Bile flow (bile-pancreatic juice), biliary excretion of total proteins, cholesterol and total lipids were measured. The single administration of different doses (25, 50 and 100 mg kg (-1)) of ginseng reduced basal bile secretion in a dose-dependent manner. Single-dose administration of ginseng at 100 mg kg(-1) caused 32.9% reduction in basal bile flow. Meanwhile, mean basal bile flow was reduced by 15.1% in rats treated with multiple doses of ginseng at 100 mg kg(-1) for two days. Biliary protein concentrations were significantly increased after single- or multiple-dose administration of ginseng, but protein output was only significantly increased (33%) in rats treated with ginseng (100 mg kg(-1)) twice a day for 2 days. Biliary total lipids and cholesterol concentration and outputs were significantly reduced after single or multiple administration of ginseng. In conclusion, administration of ginseng in the rat resulted in a reduction of bile flow and in bile secretion of total lipids and cholesterol, while it increased the secretion of proteins in a dose-dependent manner. The precise mechanisms underlying these effects remain to be elucidated. The findings indicate the need for clinical trials for the effect of this herb on bile composition and flow in man in view of a possible modulatory effect for the herb on gallstone formation.     

Hyperlipidemic guinea pig model: mechanisms of triglyceride metabolism disorder and comparison to rat

Guinea pigs and rats are both common animal models for hyperlipidemia studies. However, many recent studies have suggested that rats do not develop hypertriglyceridemia in response to cholesterol feeding. In the present work, the differences in triglyceride metabolism between guinea pigs and rats were investigated. Feeding a high-fat diet containing 0.1% cholesterol and 10% lard for 4 weeks led to a significant increase in plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and free fatty acid (FFA) in guinea pigs but not in rats. By contrast, hepatic TG levels in rats were greatly increased in response to the high-fat diet, while it remained unchanged in guinea pigs. Furthermore, the hepatic acyl CoA:diacylglycerol acyltransferase (DGAT) activity and microsomal triglyceride transfer protein (MTTP) mRNA levels in guinea pigs fed a high-fat diet were significantly higher than those in the control group, which implies an increased very-low-density lipoprotein (VLDL)-TG secretion rate in guinea pigs in response to a high-fat diet. Hepatic carnitine palmitoyltransferase-1 (CPT-1) activity and peroxisome proliferator-activated receptor-α (PPARα) mRNA levels were upregulated in guinea pigs, but not rats, fed a high-fat diet. These findings may explain the differences in plasma and hepatic TG concentrations between guinea pigs and rats. These results suggest that there are differences in triglyceride metabolism between the two species when fed high-fat diets.     

Cholinergic dependence of pancreatic response to cholecystokinin in rats and guinea pigs

• 1.1. Lorglumide and atropine were used to examine the role of cholinergic mechanisms in the pancreatic secretory response to cholecystokinin in two animal species.
• 2.2. Anaesthetized rats and guinea pigs with jugular vein and pancreatic cannulae were used and the bile juice was recirculated. In the rat, the treatment with lorglumide (3 μmol/kg) as well as atropine (100 μg/kg) did not have effects on basal interdigestive secretion, whereas in guinea pigs only atropine decreased the protein output (41%) and the juice flow (47%) of the basal pancreatic secretion.
• 3.3. Infusion of cholecystokinin (150 pmol/kg/hr in the rat and 50 pmol/kg/hr in the guinea pig) induced a marked increase in pancreatic juice flow and protein output compared to saline controls. Pretreatment of both rat and guinea pig with lorglumide resulted in a marked attenuation of the cholecystokinin-evoked secretory response.
• 4.4. In the rats, atropine decreased the response to infusion of cholecystokinin octapeptide while this antimuscarinic agent had no effect in the response to cholecystokinin in the guinea pigs.
• 5.5. This study supports the concept that the influence of cholinergic system in pancreatic response to cholecystokinin shows interspecific differences.

     

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 4th communication: Effects on gastrointestinal,urinary and reproductive systems and other effects

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sj?gren's syndrome. The general pharmacological properties of this drug on the gastrointestinal, urinary and reproductive systems and other tissues were investigated in mice, rats guinea pigs, rabbits and dogs. 1. Gastrointestinal system: SNI-2011 did not cause any effects on the gastrointestinal system, i.e. the intestinal transport of charcoal meal in mice, the secretion of gastric and bile juices, and the formation of ulcer induced by water immersion restraint in rats. 2. Urinary and reproductive systems: SNI-2011 augmented the spontaneous movement of rat pregnant uterus in vivo at 0.3 mg/kg i.v. or higher, and this effect was not observed in the non-pregnant uterus. SNI-2011 increased the spontaneous movement of isolated guinea pig bladder (3 x 10(-6) mol/l or higher) and increased the in vivo spontaneous movement of rat bladder (0.3 mg/kg i.v. or higher). SNI-2011 caused increases in rat urine volume, pH and urinary excretion of Na+ and Cl- at 30 mg/kg p.o. 3. Others: SNI-2011 had no effect on the vascular permeability in mice, hematological parameters and blood coagulation in rats. SNI-2011 had neither hemolytic nor anti-inflammatory effect. These results suggest that SNI-2011 has muscarinic effects on the gastrointestinal, urinary and reproductive systems and other tissues at the doses approximately 10-fold higher than the doses needed for saliva secretion.     

Guinea pigs as models to study the hypocholesterolemic effects of drugs

Guinea pigs are useful models to investigate the mechanisms of the hypocholesterolemic effects of drugs. Like humans, guinea pigs are one of the few species that carry the majority of cholesterol in LDL. This animal model has also been shown to develop atherosclerosis when challenged with hypercholesterolemic diets. In addition, plasma lipid profiles in males, females and ovariectomized guinea pigs, a model for menopause, follow similar patterns to those observed in humans. In this report, drugs aimed at lowering plasma cholesterol and triglycerides in hyperlipidemic individuals are reviewed. Studies analyzing the hypolipidemic effect of HMG-CoA reductase inhibitors, acyl CoA cholesterol acyltransferase inhibitors, fibrates, bile acid resins, apical sodium bile acid transporter inhibitors, and others show that guinea pigs and humans have comparable responses to drug therapy. In addition, results from the limited clinical reports addressing specific effects of drugs on LDL catabolism or VLDL synthesis are in agreement with observations in guinea pigs. From the review of these studies, it is apparent that the guinea pig is a useful animal model to further explore the mechanisms of action of lipid lowering drugs including effects on specific receptors and regulatory enzymes involved in cholesterol metabolism and on early atherosclerosis development. Abbreviations: ACAT, acyl-CoA:cholesterol acyltransferase; ASBT, apical sodium co-dependent bile acid transporter; ApoB, apolipoprotein B; CHD, coronary heart disease; CYP7, cholesterol 7alpha-hydroxylase; HDL, high density lipoprotein; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; FCR, free catabolic rate; LDL, low density lipoprotein; PPAR, peroxisome proliferators-activated receptor; TC, total cholesterol; TG, triglycerides; VLDL, very low density lipoprotein.