Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury

AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction(SJD) in rats with acute pancreatitis(AP) for protecting against multiple organ injury.METHODS An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group(CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD(CG + SJD) and a model group treated with SJD(MG + SJD), both of which were orally administered with SJD(5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male SpragueDawley rats were randomly divided into a CG, an AP model group(MG), and an SJD treated AP group(SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.RESULTS The MG + SJD displayed significantly shorter mean residence time(MRT) and higher clearance(CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve(AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin(IL)-6, IL-10, and tumor necrosis factor(TNF)-α levels in the MG were higher than those in the CG(P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG(P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG(P < 0.05).CONCLUSION AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro-and antiinflammatory responses, which might guide the clinical application of SJD for AP treatment.

Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis

AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloeemodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-a and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Optimal timing for the oral administration of DaCheng-Qi decoction based on the pharmacokinetic and pharmacodynamic targeting of the pancreas in rats with acute pancreatitis

AIM To identify the optimal oral dosing time of Da-Cheng-Qi decoction(DCQD) in rats with acute pancreatitis(AP) based on the pharmacokinetic and pharmacodynamic parameters.METHODS First, 24 male Sprague-Dawley rats were divided into a sham-operated group [NG(a)] and three model groups [4 h G(a), 12 h G(a) and 24 h G(a)]. The NG(a) and model groups were administered DCQD(10 g/kg.BW) intragastrically at 4 h, 4 h, 12 h and 24 h, respectively, after AP models induced by 3% sodium taurocholate. Plasma samples were collected from the tails at 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after a single dosing with DCQD. Plasma and pancreatic tissue concentrations of the major components of DCQD were determined by high-performance liquid chromatography tandem mass spectroscopy. The pharmacokinetic parameters and serum amylase were detected and compared. Second, rats were divided into a sham-operated group [NG(b)] and three treatment groups [4 h G(b), 12 h G(b) and 24 h G(b)] with three corresponding control groups [MG(b)s]. Blood and pancreatic tissues were collected 24 h after a single dosing with DCQD. Serum amylase, inflammatory cytokines and pathological scores of pancreatic tissues were detected and compared.RESULTS The concentrations of emodin, naringin, honokiol, naringenin, aloe-emodin, chrysophanol and rheochrysidin in the 12 h G(a) group were higher than those in the 4 h G(a) group in the pancreatic tissues(P < 0.05). The area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration values(AUC0→t) for rhein, chrysophanol, magnolol and naringin in the 12 h G(a) group were larger than those in the 4 h G(a) or 24 h G(a) groups. The 12 h G(a) group had a higher Cmax than the other two model groups. The IL-10 levels in the 12 h G(b) and 24 h G(b) groups were higher than in the MG(b)s(96.55 ± 7.84 vs 77.46 ± 7.42, 251.22 ± 16.15 vs 99.72 ± 4.7 respectively, P < 0.05), while in the 24 h G(b) group, the IL-10 level was higher than in the other two treatment groups(251.22 ± 16.15 vs 154.41 ± 12.09/96.55 ± 7.84, P < 0.05). The IL-6 levels displayed a decrease in the 4 h G(b) and 12 h G(b) groups compared to theMG(b)s(89.99 ± 4.61 vs 147.91 ± 4.36, 90.82 ± 5.34 vs 171.44 ± 13.43, P < 0.05). CONCLUSION Late-time dosing may have higher concentrations of the most major components of DCQD, with better pharmacokinetics and pharmacodynamics of antiinflammation than early-time dosing, which showed the late time to be the optimal dosing time of DCQD for AP.

Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis

BACKGROUND Acute pancreatitis(AP)is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction.Dachengqi decoction(DCQD)has a potential role in protecting the extrapancreatic organs,but the optimal oral administration time remains unclear.AIM To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.METHODS This study consisted of two parts.In the first part,24 rats were divided into a sham-operated group and three model groups.The four groups were intragastrically administered with DCQD(10 g/kg)at 4 h,4 h,12 h,and 24 h postoperatively,respectively.Tail vein blood was taken at nine time points after administration,and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected.Finally,the concentrations of the major DCQD components in all samples were detected.In the second part,84 rats were divided into a sham-operated group,as well as 4 h,12 h,and 24 h treatment groups and corresponding control groups(4 h,12 h,and 24 h control groups).Rats in the treatment groups were intragastrically administered with DCQD(10 g/kg)at 4 h,12 h,and 24 h postoperatively,respectively,and rats in the control groups were administered with normal saline at the same time points.Then,six rats from each group were euthanized at 4 h and 24 h after administration.Serum amylase and inflammatory mediators,and pathological scores of extrapancreatic organ tissues were evaluated.RESULTS For part one,the pharmacokinetic parameters(C max,T max,T 1/2,and AUC 0→t)of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later(12 h and 24 h)time points.For part two,delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels,and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration,while the results were similar between the treatment and corresponding control groups at 24 h after administration.CONCLUSION Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats,demonstrating that the late time is the optimal dosing time.

Pharmacodynamics of Yuebi Jiazhu Decoction on renal protection of adriamycin nephropathy rats

In the present study,we aimed to investigate the protective effect of Yuebi Jiazhu Decoction(YBJZD)on the kidney of adriamycin nephropathy(AN)rats.Rats were injected with adriamycin for modeling,except for the control group.After the successful establishment of the animal model,rats were randomly divided into the model group,YBJZD low-,medium-,and high-dose groups,and the positive group.The 24-h urine samples were collected.Biochemical indicators were monitored,and kidney tissues were collected for pathological analysis using light microscopy.The results showed that through 4 weeks of drug intervention,the urinary protein level was lower in the YBJZD and positive groups compared with the model group(P<0.05).Serum levels of BUN,SCr,and TG were significantly lower(P<0.01),and ALB was significantly higher(P<0.01)in the YBJZD and positive groups compared with the model group.Compared with the model group,the pathological injury of kidney tissue in the YBJZD and positive groups was significantly alleviated.These outcomes proved that YBJZD had a renal protective effect on AN rats.

参柏祛毒袋泡剂抗炎镇痛抑菌和药物安全性研究

目的观察参柏祛毒袋泡剂抗炎镇痛抑菌药效学和药物安全性情况。方法(1)抗炎实验:采用小鼠耳廓肿胀法,选取昆明小鼠60只,体质量18~24 g,按体质量分层使用随机数字表分为空白组、参柏高剂量组(1.750 g生药/mL)、参柏中剂量组(0.875 g生药/mL)、参柏低剂量组(0.438 g生药/mL)、阿司匹林组(100 mg/kg)5组,每组12只。涂抹70μL二甲苯在预先给药的小鼠右耳上,处死后对比左右耳片重量,计算肿胀度。(2)镇痛实验:采用热板致痛法,选取昆明小鼠48只,雌性,体质量18~24 g,按体质量分层使用随机数字表随机分成空白组、参柏高剂量组(1.750 g生药/mL)、参柏中剂量组(0.875 g生药/mL)、参柏低剂量组(0.438 g生药/mL)4组,每组12只。测定小鼠基础痛阈,再以40℃药浴各组分别泡足20 min,测量给药后5个时间点小鼠痛阈,计算痛阈提高百分率。(3)体外抑菌实验:将观察药制备成原液、1∶1、1∶2、1∶4、1∶85个浓度梯度,分别加入5种共25菌株,培养后读取各组最低抑菌浓度值。(4)安全性实验:采用家兔皮肤刺激性实验,选取健康大耳白家兔16只,使用随机数字表随机分为单次给药正常皮肤组、破损皮肤组及多次给药正常皮肤组、破损皮肤组4组,造模破损皮肤组,一侧去毛区涂参柏祛毒袋泡剂0.5 mL,另一侧对照区涂等量蒸馏水作空白对照,单次给药(1次/d)和多次给药(1次/d,连续7 d)进行对比,观察皮肤刺激性。采用实验家兔皮肤急毒实验,选取新西兰家兔24只,使用随机数字表随机分为完整组和破损皮肤组,每组再随机分为参柏高、低剂量及空白组,共6组,药物均匀涂抹于家兔背部除毛区,于去掉受试药物后1、24、48、72 h至14 d,每日观察动物皮肤及全身情况做出评价。结果(1)抗炎实验结果提示,参柏祛毒袋泡剂对二甲苯所致小鼠耳廓肿胀有显著抑制作用,参柏高、中剂量组小鼠耳廓肿胀度低于空白组,差异有统计学意义(P<0.05,P<0.01)。(2)镇痛实验结果提示,参柏祛毒袋泡剂对热刺激所致小鼠疼痛有明显的镇痛作用,参柏高剂量组给药后0.5~4.5 h较空白组小鼠痛阈高(P<0.05,P<0.01),参柏中剂量组给药后1.5~3.5 h较空白组小鼠痛阈高(P<0.05)。(3)体外抑菌实验结果提示,参柏祛毒袋泡剂对铜绿假单胞菌、金黄色葡萄球菌、白色念珠菌、大肠埃希氏菌、肺炎克雷伯菌有不同程度的抑制作用,且对铜绿假单胞菌、金黄色葡萄球菌的抑制作用最强。(4)安全性实验结果提示,参柏祛毒袋泡剂对家兔正常皮肤和破损皮肤,单次给药和多次给药均无皮肤刺激性,与空白组比较差异无统计学意义(P>0.05);对家兔完整皮肤和破损皮肤组给药,观察至14 d,均无不良反应,参柏高、低剂量组与空白组比较差异无统计学意义(P>0.05)。结论参柏祛毒袋泡剂具有明显的抗炎、镇痛、抑菌作用,且药物外用安全。

舒肺压方单煎与合煎的成分差异及对肺动脉高压的影响

目的:探讨舒肺压方单煎、合煎成分特征及对肺动脉高压的改善作用。方法:通过超高效液相色谱-质谱法(UPLC-MS/MS)对舒肺压方单煎及合煎的成分进行定性、定量分析,明确不同煎煮法对舒肺压方成分特征的影响,并基于野百合碱诱导的大鼠肺动脉高压,观察舒肺压方单煎及合煎对肺动脉高压的改善作用。结果:舒肺压方单煎液及合煎液中均检出707种成分,单煎液与合煎液成分种类一致;其中644种成分含量无明显差异,63种成分含量具有显著差异;与单煎液比较,合煎液中有46种成分含量明显上调,17种成分含量明显下调;舒肺压方合煎较单煎可明显降低大鼠平均肺动脉压,改善肺部组织病理学损伤。结论:舒肺压方不同煎煮方式可影响其成分特征,合煎较单煎对野百合碱诱导的大鼠肺动脉高压的改善作用更显著。

食消饮改善食积小鼠的药效作用研究

目的探讨食消饮对食积小鼠的药效作用。方法将120只ICR小鼠随机均分为两个实验(实验A和B),每个实验的小鼠均分为正常组,模型组,食消饮低、中、高剂量组和健胃消食片组。食积模型构建后,各给药组灌胃相应受试药物,每日2次,连续7 d。其中实验A小鼠用于脏器系数、血清生化指标、小肠免疫组化、结肠HE染色以及肠道菌群的检测,实验B小鼠用于胃排空率和小肠推进率实验。结果与模型组相比,食消饮高剂量组小鼠脾脏脏器系数明显升高,中、高剂量组小鼠血清生化指标均得到明显改善,小肠推进率升高、胃内残留率降低。免疫组化结果显示,食积模型小鼠小肠中C-kit表达明显降低,食消饮中、高剂量和健胃消食片组小鼠中C-kit表达明显升高。HE结果显示,食消饮中、高剂量组小鼠结肠绒毛长度均增加、隐窝深度均降低、绒毛长度/隐窝深度的比值增加。粪便菌群计数结果显示,食消饮高剂量组小鼠粪便中乳杆菌和双歧杆菌增加,肠杆菌、肠球菌和产气荚膜梭菌均减少。结论食消饮能通过调控小肠C-kit表达、胃肠动力相关激素分泌、肠道菌群丰度、肠道黏膜结构等改善食积模型小鼠的胃肠动力与功能。

逆乌茜草水煎液抗炎、镇痛和止泻作用研究

为了确证逆乌茜草水煎液的抗炎作用、镇痛作用、止泻作用,按照试验设计将210只昆明小鼠随机分组,逆乌茜草水煎液组分别灌胃低剂量(0.3033 g/kg)、中剂量(0.9100 g/kg)、高剂量(2.7300 g/kg)的逆乌茜草水煎液,同时每个试验设立模型对照组和阳性对照组。分别采用二甲苯致小鼠耳肿胀法、醋酸致小鼠疼痛扭体法、炭末推进测定法和粪便含水量称重法对逆乌茜草水煎液进行抗炎、镇痛、涩肠和止泻作用研究。结果表明,与模型组比较,逆乌茜草水煎液中剂量组二甲苯引起的耳廓肿胀率极显著降低(P<0.01),表明逆乌茜草水煎液具有良好的抗炎作用,并能延长醋酸致小鼠疼痛扭体潜伏期,但作用不显著,中剂量组、高剂量组小鼠疼痛扭体次数显著减少(P<0.05或P<0.01),且随药物剂量增大,小鼠疼痛扭体抑制率明显升高,表明逆乌茜草水煎液具有显著的镇痛作用;低剂量组、中剂量组、高剂量组逆乌茜草水煎液能抑制炭末在小鼠小肠内的推动,说明逆乌茜草水煎液具有一定的涩肠作用;与空白对照组比较,给药3 d,逆乌茜草水煎液低剂量组、中剂量组、高剂量组和阳性对照组小鼠粪便中含水量无显著性差异(P>0.05),表明逆乌茜草水煎液具有良好的止泻作用。综上,逆乌茜草水煎液具有显著的抗炎作用、镇痛作用和止泻作用,且具有一定的涩肠作用,可作为犊牛腹泻潜在的候选治疗药物进行研究开发。

两种不同取血部位制备桂枝汤含药血清对其抗炎作用影响差异的研究

目的基于两种不同取血部位制备桂枝汤含药血清,探讨其抗炎作用差异。方法取雄性SD大鼠按10倍临床剂量给药(桂枝汤汤剂生药1 g/mL),取门静脉血、外周血含药血清,采用快速液相-三重四级杆质谱联用仪(rapid resolution liquid chromatography-triple quadrupole mass spectrometry,RRLC-QQQ-MS/MS),建立桂枝汤汤剂、含药血清中8种化学成分含量测定方法,并对含量进行测定。取对数生长期小鼠脑微血管内皮细胞(brain-derived endothelial cells.3,bEnd.3)模型,用白细胞介素(interleukin,IL)-1β刺激,建立细胞炎症模型,使用bEnd.3细胞作为正常组。除正常组、模型组外,设置桂枝汤汤剂高、中、低剂量组(分别含5%、2.5%、1.25%桂枝汤汤剂),门静脉含药血清高、中、低剂量组(分别含20%、10%、5%门静脉含药血清)和外周血含药血清高、中、低剂量组(分别含20%、10%、5%外周血含药血清),ELISA法测定细胞外液中的前列腺素(prostaglandin,PG)E_(2)含量。结果含量测定结果显示汤剂中芍药苷、芍药内酯、甘草苷、甘草酸比例相对较高,血清中肉桂酸、6-姜酚含量相对较高,较汤剂中新出现甘草次酸等代谢物。门静脉血清中以上8种化合物含量均高于外周血血清。5%桂枝汤汤剂中甘草酸含量为798.13 ng/mL,20%门静脉含药血清中甘草酸含量为316.22 ng/mL,20%外周血中甘草酸含量为481.17 ng/mL,药物中成分的含量在同一数量级。与模型组比较,将高、中、低剂量桂枝汤汤剂添加到bEnd.3细胞培养体系中,高、中、低剂量桂枝汤组细胞外液中PGE_(2)的水平均明显高于模型组(P<0.05),而门静脉或外周血含药血清组细胞外液中PGE_(2)的水平均明显低于模型组(P<0.05),且门静脉血清的药效作用显著强于相同浓度的外周血血清(P<0.05)。结论桂枝汤汤剂经胃肠道给药后,门静脉含药血清相较外周血含药血清显示出更高的成分含量与抗炎作用。这一发现提示采用门静脉含药血清而非传统的外周血含药血清在中药方剂研究中的重要性。

黄鹤汤治疗肺脾气虚型变应性鼻炎的疗效观察

目的 观察黄鹤汤治疗肺脾气虚型变应性鼻炎的临床疗效。方法 肺脾气虚型变应性鼻炎患者177例,随机分为西药治疗组59例、中药治疗组60例和联合用药组58例。西药组予氯雷他定口服,中药组予黄鹤汤口服,联合用药组同时给予黄鹤汤及氯雷他定口服。均以14天为1疗程,连续用药3疗程。疗程结束后,所有患者均随访1年。同时,分别于治疗开始前、疗程结束时及随访期结束时检测血清Ig E以及细胞因子IL-4与IFN-γ水平。然后,比较分析各组患者治疗前、治疗后、随访期的临床症状评分及总有效率,以及各组血清Ig E及细胞因子IL-4,IFN-γ水平的变化趋势。结果 治疗结束时,西药治疗组总有效率52.5%,中药治疗组总有效率71.6%,联合治疗组为93.1%,差异具有显著性统计学意义(P<0.05)。随访期结束时,西药组总有效率37.2%,中药组总有效率58.3%,联合治疗组总有效率82.7%,中药组及联合用药组远期疗效均优于西药组(P<0.05)。中药组及联合用药组Ig E及IL-4降低水平、IFN-γ提升效率均优于西药组(P<0.05)。三组的药物不良反应差异均无统计学意义(P>0.05)。结论 黄鹤汤治疗肺脾气虚型变应性鼻炎疗效确切,联合应用抗组胺药会进一步提升疗效水平且无明显毒副作用。

中药配方颗粒药效学及与饮片药效比较研究进展

目的对中药配方颗粒的药效学及与饮片药效比较研究进展进行综述。方法通过查阅近十年国内相关文献,从相关疾病类型、药方种类、病理模型、造模方法、阳性对照药、检测指标等方面进行归纳总结。结果以中药配方颗粒与中药饮片药效比较研究为主,涉及结肠炎、慢性胃炎、高血脂症、关节炎、恶性肿瘤、糖尿病、感冒等疾病和湿困脾胃证、肾阴虚证、阳明腑实证等中医病证。结论中药配方颗粒作为新型饮片应用于中医临床,在药效上是否与传统饮片等效仍然存在争议。本文详细综述了中药配方颗粒的药效学及与饮片药效比较研究,对所存在的问题进行分析,并对未来发展进行展望。

加味过敏煎对Ⅰ型超敏反应的药效及其作用机制的研究

目的 研究加味过敏煎调控Ⅰ型超敏反应大鼠药效及作用机制,以明确加味过敏煎治疗Ⅰ型超敏反应免疫分子机制及作用靶点。方法 通过卵白蛋白(OVA)建立Ⅰ型超敏反应大鼠模型。将造模成功的动物分为模型组、地塞米松阳性对照组(8.4×10^(-5) g/kg)、加味过敏煎高、中、低剂量组(25.44 g/kg、12.72 g/kg、6.36 g/kg)。另设不造模的空白组。末次给药后,测定大鼠血清中免疫球蛋白E(IgE)、组胺、白介素-4(interleukin-4,IL-4)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)的因子含量;RT-PCR法测定大鼠脾脏中IFN-γ、T细胞中T-box(T-box expressed in T cells, T-bet)、IL-4、GATA结合蛋白3(GATA family of transcription factors3, GATA3)、白细胞介素-17(interleukin-17,IL-17)、白细胞介素-10 (interleukin-10,IL-10)、叉头状转录因子P3(forkhead box protein-3, FOXP3)的mRNA表达水平。结果 与模型组比较,加味过敏煎高、中剂量组明显降低Ⅰ型超敏反应大鼠血清中IgE(P<0.01,P<0.05)、组胺含量(P<0.05),升高IFN-γ水平(P<0.05),并且高剂量组能有效降低血清中IL-4水平(P<0.05);RT-PCR结果显示,与模型组比较,加味过敏煎高、中、低剂量组可以上调I型超敏反应大鼠脾组织T-bet(P<0.05,P<0.01)、IL-10(P<0.05)、FOXP3(P<0.05) mRNA表达,高、中剂量组显著促进IFN-γ mRNA表达(P<0.05)。同时加味过敏煎高、中、低剂量组下调IL-17mRNA表达(P<0.05),高剂量组显著抑制IL-4、GATA3 mRNA表达(P<0.05)。结论 加味过敏煎可以通过调节Th1/Th2细胞、Th17/Treg细胞平衡抑制炎症反应,进而影响免疫功能,达到抑制Ⅰ型超敏反应的作用。

Pharmacodynamic study on insomnia-curing effects of Shuangxia Decoction in Drosophila melanogaster

The present study aimed to establish a pharmacodynamic method using the py Solo software to explore the influence of freeze-dried powders of Shuangxia Decoction(SXD) on the sleep of normal Drosophila melanogaster and the Drosophila melanogaster whose sleep was divested by light. The dose-effect and the time-effect relationships of SXD on sleep were examined. The effect-onset concentration of SXD was 0.25%, the plateau appeared at the concentration of 2.5% and the total sleep time showed a downtrend when the concentration was greater than 2.5%. The sleep time was the longest on the fourth day after SXD was given. The fruit fly sleep deprivation model was repeated by light stimulation at night. The middle dosage group(2.5%) had the best insomnia-curing effect. In conclusion, using the py Solo software, an approach for the pharmacodynamics study was established with Drosophila melanogaster as a model organism to determine the insomnia-curing effects of the traditional Chinese medicine(TCM). Our results demonstrated the reliability of this method. The freeze-dried powders of SXD could effectively improve the sleep quality of Drosophila melanogaster.

增液汤及其药效组分改善2型糖尿病大鼠的药理作用研究

目的研究增液汤及其药效组分对2型糖尿病(Diabetes mellitus type 2,T2DM)大鼠血糖、血脂、血清胰岛素及T2DM疾病关键靶点的影响。方法采用高脂饮食联合腹腔注射链脲佐菌素构建T2DM模型。将造模成功的大鼠随机分为模型组、二甲双胍组、增液汤药效组分等剂量组、增液汤药效组分高剂量组和增液汤组。检测血糖血脂水平和FGF1、VEGFA等T2DM疾病关键靶点表达;采用苏木精-伊红染色法观察大鼠胰腺组织病理形态学。结果增液汤组和增液汤药效组分等剂量组T2DM大鼠摄食量显著降低,空腹血糖值、糖化血清蛋白水平、血脂水平和胰岛素抵抗指数显著降低,血清胰岛素和胰岛素敏感指数显著升高;其中,增液汤药效组分等剂量组糖口服耐量显著降低。增液汤组和增液汤药效组分等剂量组、高剂量组外分泌腺腺泡病变减轻,且血清FGF1、VEGFA水平显著提高,增液汤组血清Galectin-3水平显著降低。结论增液汤及其药效组分对T2DM大鼠均具有降血糖作用,其作用机制可能与降低血糖水平、调节血脂代谢、提高胰岛素敏感性及修复胰腺组织相关。

芪七连胶囊两种不同制备工艺对剂型成型的影响及药效评价研究

目的:改进芪七连胶囊的提取工艺和制备工艺,并进行药效学评价。方法:以粒度分布、休止角、吸湿率、胶囊的装量差异为评价指标,对比两种制备工艺(乙醇回流提取法和水煎法)对芪七连胶囊成型的影响,并以自发性高血压大鼠(SHR)为模型,对所得的芪七连胶囊成品的降压和血管内皮保护作用进行评价。结果:分别以10倍量、8倍量的50%乙醇回流提取方中黄芪、黄连、黄柏、蒲黄、杜仲、钩藤药材2次,第1次2 h,第2次1 h,减压干燥后加入三七细粉,制粒后填充胶囊。其粒度分布、休止角、吸湿率、胶囊的装量差异均优于原工艺(水煎法)。药效学实验表明,新工艺所制芪七连胶囊成品,给与临床使用量,可明显降低SHR大鼠的血压,且具有保护血管内皮细胞作用,其药效优于原工艺成品(P<0.05或P<0.01)。结论:新工艺的制备工艺可行、稳定,所制得成品具有明显的降压及保护血管内皮的作用。

身痛逐瘀汤对CIA模型大鼠预防及治疗的作用研究

目的 探究身痛逐瘀汤对胶原诱导Lewis大鼠关节炎模型(CIA模型)大鼠的预防效果及治疗作用。方法 将42只大鼠随机分为空白组,模型组,甲氨蝶呤组(0.9 mg·kg^(-1)),预防给药组(身痛逐瘀汤,9 g·kg^(-1)),身痛逐瘀汤低(4.5 g·kg^(-1))、中(9 g·kg^(-1))、高(18g·kg^(-1))剂量组,每组6只,除空白组外,其余各组使用胶原对Lewis大鼠进行二次免疫构建CIA模型。实验中每周两次记录动物状态、关节炎评分、足容积及痛阈值,实验终点检测大鼠血液流变学变化,使用ELISA法测定大鼠血清中IL-10、TGF-β、IL-17、TNF-α、MMP1、MMP13、RANKL的表达,使用HE染色、番红固绿染色观察其踝关节组织的病理变化并进行组织病理学评分。结果 与模型组相比,身痛逐瘀汤各剂量组的关节炎评分、痛阈值、足肿胀率均降低,其中身痛逐瘀汤中、高剂量组效果显著;身痛逐瘀汤中、高剂量组的低、中、高切全血黏度,血浆黏度、血沉及血沉方程K值显著降低;各剂量组促进抑炎因子IL-10的表达升高,促炎因子TGF-β、IL-17、TNF-α的表达降低,抑制骨损伤相关炎症因子MMP-1、MMP-13、RANKL的含量,减轻病理损伤,高剂量组治疗效果显著;身痛逐瘀汤预防给药组在大鼠关节炎评分、痛阈值、足肿胀率、血清炎症因子及病理切片的结果均优于身痛逐瘀汤各治疗剂量组。结论 身痛逐瘀汤对CIA模型大鼠具有良好的预防效果及治疗作用,可以有效缓解大鼠的关节炎症状,减轻疼痛,改善血液流变,抑制炎症,改善病理损伤。

健脾消渴方改善2型糖尿病大鼠药效学研究

目的评价健脾消渴方对2型糖尿病大鼠的药效,并探讨其可能的作用机制。方法40只SD大鼠随机分为正常对照组、模型对照组、健脾消渴方组及盐酸二甲双胍组,每组10只,STZ+高脂饮食建立2型糖尿病大鼠模型,给予相应药物,持续4周。实验结束后取材,考察大鼠空腹血糖变化情况;ELISA法检测大鼠血清中白细胞介素-1(interleukin-1β,IL-1β)、白细胞介素-10(interleukin-10,IL-10)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、D-氨基酸氧化酶(D-amino acid oxidase,DAO)、D-乳酸含量;考察血清血脂四项[甘油三酯(triglycerides,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)]含量;HE染色法观察各组大鼠胰腺及回肠的组织形态学改变;免疫荧光法检测大鼠回肠L细胞的免疫荧光法检测大鼠回肠L细胞的胰高糖素样肽-1(glucagon-like peptide-1,GLP-1)阳性表达;Western blotting法检测大鼠结肠组织中紧密连接蛋白(occludin)、闭锁小带蛋白-1(zonula occludens-1,ZO-1)、黏蛋白2(Muc2)蛋白相对表达。结果健脾消渴方可有效降低2型糖尿病大鼠的空腹血糖,下调血清中IL-1β、TNF-α含量,上调IL-10含量,抑制DAO、D-乳酸含量;同时,显著性下调TG、TC、LDL-C含量,但在提高HDL-C含量方面上仅具有趋势性;此外,健脾消渴方可改善大鼠胰腺及回肠损伤,提高GLP-1阳性表达,并有效降低2型糖尿病大鼠结肠occludin、ZO-1、Muc2蛋白相对表达。结论健脾消渴方对2型糖尿病大鼠具有较好的治疗效果,其作用可能与改善血清炎症、调节血脂,减轻肠道功能损伤,改善肠道屏障通透性与保护肠道屏障生理结构等作用有关。

泻心汤在急性炎症动物模型上的抗炎效应

目的研究泻心汤的抗炎效应及抗炎作用的机制。方法采用4种急性炎症模型,包括大鼠角叉菜胶及蛋清足肿胀、2%冰醋酸小鼠腹腔渗出和小鼠内毒素急性肺损伤模型,观察泻心汤对动物实验性急性炎症模型的影响;并观察小鼠内毒素急性肺损伤模型中,泻心汤对血浆一氧化氮合成酶、一氧化氮、肿瘤坏死因子-α及自由基产物丙二醛的影响。结果泻心汤ig给药后对上述4种炎症模型都具有良好的抗炎效果;并可以抑制内毒素炎症过程中诱生型一氧化氮合成酶的活性,抑制一氧化氮、肿瘤坏死因子-α等炎症因子的产生,减少自由基产物丙二醛生成。结论泻心汤具有良好的抗炎效应,且可以通过多途径产生抗炎作用。

黄连解毒汤传统饮片汤剂与配方颗粒汤剂药效学对比研究

目的对黄连解毒汤传统饮片汤剂与配方颗粒汤剂进行药效学比较,为黄连解毒汤配方颗粒汤剂的临床应用提供理论依据。方法从对二甲苯致小鼠耳廓肿胀、新鲜鸡蛋清致大鼠足跖肿胀和2,4-二硝基苯酚致大鼠发热三个方面的影响,考察黄连解毒汤传统饮片汤剂与配方颗粒汤剂药效的差异。结果传统饮片汤剂与配方颗粒汤剂均能减轻二甲苯致小鼠耳廓肿胀和新鲜蛋清致大鼠足跖肿胀,且两种汤剂等剂量间的抗炎作用无显著性差异(P>0.05)。而不同剂量组的传统饮片汤剂和配方颗粒汤剂对2,4-二硝基苯酚致大鼠发热均有不同程度的解热作用,其中,两者的中、高剂量组优于低剂量组(P<0.05),且等剂量的配方颗粒组优于传统饮片组(P<0.05)。结论黄连解毒汤配方颗粒汤剂药效相似或优于传统饮片汤剂。