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葛根素和清开灵注射液在清醒Beagle犬的类过敏反应检测及其机制探讨

发布时间:2019-03-03 20:13
【摘要】:随着葛根素注射液和清开灵注射液在临床上的广泛应用,其不良反应的报道逐年增多,严重的有可能导致过敏性休克甚至死亡。二者引发的过敏反应中有相当一部分是首次给药,且发生在给药30min内,表现为明显的类过敏反应特征。 类过敏的临床反应症状与Ⅰ型过敏反应相似,主要表现为恶心、呕吐、腹痛腹泻、荨麻疹、血管性水肿、过敏性哮喘等,然而其发生机制与过敏反应不同,故而被称为“类过敏反应”。与Ⅰ型过敏反应比较,类过敏反应为首次接触致敏原即可引发过敏样症状,不需要免疫球蛋白介导,而是直接刺激肥大细胞或嗜碱性粒细胞脱颗粒释放过敏性介质导致的。 建立类过敏反应评价模型对清开灵注射液和葛根素注射液进行类过敏反应评价对降低临床中用药风险具有重要的意义,本实验室己建立的模型有麻醉Beagle犬类过敏反应检测模型等,本研究在其基础上进一步改善实验方法,通过DSI清醒动物生理信号遥测系统建立清醒Beagle犬类过敏反应检测模型,对清开灵注射液和葛根素注射液引起的类过敏反应进行评价;分离犬外周血单个核细胞(peripheral blood mononuclear cell, PBMC),评价清开灵注射液和葛根素注射液对细胞因子的影响,探讨类过敏反应与细胞因子的关系。 1清醒Beagle犬类过敏反应检测模型的建立 目的:建立清醒Beagle犬类过敏反应检测模型,并用Tween80和Compound48/80评价该模型的可行性。方法:通过Beagle犬的植入手术,将遥测系统的植入子植入犬的体内,手术恢复后,经静脉推注分别给予犬Compound48/80和0.05%、0.1%、0.2%、0.5%的Tween80,采用Dataquest A.R.T.4.3系统连续监测给药过程中及给药后Beagle犬血压和心率的变化并观察犬的体征变化,研究血压和心率作为该类过敏反应检测指标的灵敏性。结果:Tween80和Compound48/80给药后犬出现骚动、皮肤潮红、巩膜充血等类过敏反应症状,且血压出现不同程度的下降,心率加快。结论:建立的清醒Beagle犬类过敏反应检测模型具有良好的可行性,血压、心率及犬的体征变化可作为该模型灵敏的检测指标。 2对清开灵注射液及葛根素注射液的致类过敏反应进行评价 目的:利用清醒Beagle犬类过敏反应检测模型对清开灵注射液及葛根素注射液进行评价,研究二者在清醒犬引发的类过敏反应情况。方法:分别经静脉滴注以120mL·h-1的给药速度给予犬不同浓度的清开灵注射液和葛根素注射液,采用Dataquest A.R.T.4.3系统连续监测给药过程中及给药后Beagle犬血压和心率的变化并观察犬的体征变化。结果:1.2mL·kg-1,2.3mL·kg-1,11.5mL·kg-1清开灵注射液对犬血压和心率均未产生明显的影响,Beagle犬也未出现明显的体征变化;0.24mL·kg-1葛根素注射液对犬血压和心率的影响不明显,而0.47mL·kg-1葛根素注射液引起犬血压明显降低,平均动脉压在药后30min时从药前的(115.35±7.73)mmHg降低到(91.74±10.18) mmHg (n=4, P0.01),收缩压从药前的(147.33±14.65)mmHg降低到(112.88±6.51) mmHg (n=4, P0.01),但未见明显的体征变化,心率变化也不明显。结论:120mL·h-1的给药速度下清开灵注射液未引起清醒Beagle犬发生类过敏症状;葛根素注射液可使清醒犬的血压降低,并与剂量相关。 3利用犬PBMC评价清开灵注射液和葛根素注射液对细胞因子的影响及类过敏反应与细胞因子的关系 目的:初步探究清开灵注射液和葛根素注射液对Beagle犬细胞因子的影响,研究类过敏反应与细胞因子之间的关系。方法:通过梯度密度离心法分离犬PBMC,分别与类过敏阳性药Compound48/80及Tween80、清开灵注射液、葛根素注射液充分进行反应后利用相应的犬细胞因子ELISA试剂盒测定PBMC释放的细胞因子水平,主要测定的细胞因子为IFN-γ、TNF-α、IL-6。结果:Compound48/80与Tween80使PBMC分泌的TNF-α水平下降,清开灵注射液组和葛根素注射液组的TNF-α水平也出现了明显的下降,且具有统计学意义上的显著性差异PBMC与各组药物反应后分泌的IFN-γ水平有不同程度的下降,其中清开灵注射液引起的下降最为明显。对IL-6的浓度进行检测,检测结果显示各组的吸光度值均小于标准对照组的最小值,因此所测结果无意义。结论:Compound48/80, Tween80以及清开灵注射液和葛根素注射液可引起犬细胞因子IFN-γ、 TNF-α的分泌量减少。
[Abstract]:With the wide application of the puerarin injection and the Qingkailing injection, the report of the adverse reaction has increased year by year, which may cause anaphylactic shock and even death. A significant portion of the allergic reaction induced by the two was the first dose, and occurred within 30 minutes of the administration, showing an apparent allergic response characteristic. The clinical response of an allergic reaction is similar to that of the type I, and is mainly characterized by nausea, vomiting, abdominal pain, diarrhea, urticaria, angioedema, allergic asthma, etc. However, the pathogenesis is different from that of the allergic reaction, thus being referred to as" trunk> "Anaphylactic reaction" . Compared with type I allergic reaction, the allergic reaction is the first time the allergic reaction is caused by the allergic reaction, which is not required to be mediated by the immunoglobulin, but is directly stimulated by the mast cell or the basophil degranulation and release of the allergic medium. It is of great significance for the evaluation of the allergic reaction of the Qingkailing injection and the puerarin injection to reduce the risk of drug use in the clinical. The model established in this lab is the sensitive detection of the Anesthetic Beagle dogs. In this study, the experimental method was further improved on the basis of this study, and a clear Beagle dog type allergic reaction detection model was established through the DSI conscious animal physiological signal telemetry system, and the allergic reaction caused by the Qingkailing injection and the puerarin injection Objective To evaluate the effect of Qingkailing injection and puerarin injection on the cytokines in the peripheral blood mononuclear cells (PBMC) of the dog. Relationship.1 Conscious Beagle dog type allergic reaction test The purpose of establishing the model is to establish a model of the sensitive response of the conscious Beagle dogs and to evaluate the model with the Tween80 and the Compound48/80. The method comprises the following steps of: implanting the implanted sub-implant of the telemetry system into the body of a dog through an implantation operation of a Beagle dog, and respectively giving the dog Compound48/80 and 0.05%, 0.1%, 0.2% and 0.5% by a vein injection after the operation is recovered; The changes in blood pressure and heart rate in Beagle dogs were continuously monitored and observed in Beagle dogs following administration of Tween80 and the changes in blood pressure and heart rate in Beagle dogs following administration, and blood pressure and heart rate were studied as such an allergic reaction The results showed that after the administration of Tween80 and Compound48/80, there was a commotion of the dog, the skin became red and the sclera was hyperemia and the like, and the blood pressure had different degrees. Conclusion: The model has good feasibility, and changes of blood pressure, heart rate and dog's sign can be used as the model. sensitive detection index.2. Qingkailing injection and puerarin injection The purpose of the evaluation of the allergic reaction was to evaluate the Qingkailing injection and the puerarin injection by using the response detection model of the conscious Beagle dogs. Methods: The blood pressure and heart rate of Beagle dogs in Beagle dogs were continuously monitored by using the dataquest A.R. T.4.3 system at different concentrations of 120 mL 路 h-1. The results were as follows: 1.2 mL 路 kg-1, 2.3 mL 路 kg-1, 11.5 mL 路 kg-1 Qingkailing Injection had no significant effect on the blood pressure and heart rate of the dog, and no obvious change of the sign was observed in Beagle dog. The effect of 0.24 mL 路 kg-1 puerarin injection on the blood pressure and heart rate of the dog was not obvious, and 0.47 mL 路 kg-1 puerarin injection The blood pressure of the dog was significantly lower than that of the injection (115.35-7.73) mmHg (91.74 to 10.18) mmHg (n = 4, P0.01), and the systolic blood pressure was decreased to (112.88 to 6.51) mmHg (n = 4, P0.01), but no significant signs were found. The change of the heart rate is not obvious. Conclusion: The Qingkailing injection at 120 mL 路 h-1 does not cause an allergic symptom of the conscious Beagle dog, and the puerarin injection can be used for the conscious dog. Blood pressure reduction and dose-related. The effect of Qingkailing injection and puerarin injection on cytokines was evaluated by using PBMCs. Objective: To investigate the relationship between the allergic reaction and the cytokines: the preliminary study of the Qingkailing injection and the puerarin injection Effects of Cytokine on Beagle Dogs The relationship between the allergic reaction and the cytokines was determined by gradient-density centrifugation. The peripheral blood mononuclear cells were isolated by gradient-density centrifugation, and the corresponding canine cytokine-linked immunosorbent assay (ELISA) kit was used for the sufficient reaction of the anti-allergic positive drug, the Compound48/80 and the Tween 80, the Qingkailing injection and the puerarin injection. The cytokine levels released from PBMCs were determined, with the primary measured cytokine of I Results of FN-1, TNF-1, and IL-6. Results: The levels of TNF-1, Qingkailing injection group and puerarin injection group were decreased by Compound48/80 and Tween80. There was also a significant decrease in the level of NF-1, and there was a statistically significant difference in the level of IFN-1 secreted by PBMCs after the reaction of the groups, of which The effect of Qingkailing injection was the most obvious. The concentration of IL-6 was detected. The results showed that the absorbance of the group was less than that of the standard control. Conclusion: Compounded 48/80, Tween80 and Qingkailing injection and puerarin injection can cause cytokine IF in dogs.
【学位授予单位】:山东大学
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R725.9

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