葛根素和清開靈注射液在清醒Beagle犬的類過敏反應(yīng)檢測(cè)及其機(jī)制探討
發(fā)布時(shí)間：2019-03-03 20:13
【摘要】：隨著葛根素注射液和清開靈注射液在臨床上的廣泛應(yīng)用,其不良反應(yīng)的報(bào)道逐年增多,嚴(yán)重的有可能導(dǎo)致過敏性休克甚至死亡。二者引發(fā)的過敏反應(yīng)中有相當(dāng)一部分是首次給藥,且發(fā)生在給藥30min內(nèi),表現(xiàn)為明顯的類過敏反應(yīng)特征。 類過敏的臨床反應(yīng)癥狀與Ⅰ型過敏反應(yīng)相似,主要表現(xiàn)為惡心、嘔吐、腹痛腹瀉、蕁麻疹、血管性水腫、過敏性哮喘等,然而其發(fā)生機(jī)制與過敏反應(yīng)不同,故而被稱為“類過敏反應(yīng)”。與Ⅰ型過敏反應(yīng)比較,類過敏反應(yīng)為首次接觸致敏原即可引發(fā)過敏樣癥狀,不需要免疫球蛋白介導(dǎo),而是直接刺激肥大細(xì)胞或嗜堿性粒細(xì)胞脫顆粒釋放過敏性介質(zhì)導(dǎo)致的。 建立類過敏反應(yīng)評(píng)價(jià)模型對(duì)清開靈注射液和葛根素注射液進(jìn)行類過敏反應(yīng)評(píng)價(jià)對(duì)降低臨床中用藥風(fēng)險(xiǎn)具有重要的意義,本實(shí)驗(yàn)室己建立的模型有麻醉Beagle犬類過敏反應(yīng)檢測(cè)模型等,本研究在其基礎(chǔ)上進(jìn)一步改善實(shí)驗(yàn)方法,通過DSI清醒動(dòng)物生理信號(hào)遙測(cè)系統(tǒng)建立清醒Beagle犬類過敏反應(yīng)檢測(cè)模型,對(duì)清開靈注射液和葛根素注射液引起的類過敏反應(yīng)進(jìn)行評(píng)價(jià)；分離犬外周血單個(gè)核細(xì)胞(peripheral blood mononuclear cell, PBMC),評(píng)價(jià)清開靈注射液和葛根素注射液對(duì)細(xì)胞因子的影響,探討類過敏反應(yīng)與細(xì)胞因子的關(guān)系。 1清醒Beagle犬類過敏反應(yīng)檢測(cè)模型的建立 目的：建立清醒Beagle犬類過敏反應(yīng)檢測(cè)模型,并用Tween80和Compound48/80評(píng)價(jià)該模型的可行性。方法：通過Beagle犬的植入手術(shù),將遙測(cè)系統(tǒng)的植入子植入犬的體內(nèi),手術(shù)恢復(fù)后,經(jīng)靜脈推注分別給予犬Compound48/80和0.05%、0.1%、0.2%、0.5%的Tween80,采用Dataquest A.R.T.4.3系統(tǒng)連續(xù)監(jiān)測(cè)給藥過程中及給藥后Beagle犬血壓和心率的變化并觀察犬的體征變化,研究血壓和心率作為該類過敏反應(yīng)檢測(cè)指標(biāo)的靈敏性。結(jié)果：Tween80和Compound48/80給藥后犬出現(xiàn)騷動(dòng)、皮膚潮紅、鞏膜充血等類過敏反應(yīng)癥狀,且血壓出現(xiàn)不同程度的下降,心率加快。結(jié)論：建立的清醒Beagle犬類過敏反應(yīng)檢測(cè)模型具有良好的可行性,血壓、心率及犬的體征變化可作為該模型靈敏的檢測(cè)指標(biāo)。 2對(duì)清開靈注射液及葛根素注射液的致類過敏反應(yīng)進(jìn)行評(píng)價(jià) 目的：利用清醒Beagle犬類過敏反應(yīng)檢測(cè)模型對(duì)清開靈注射液及葛根素注射液進(jìn)行評(píng)價(jià),研究二者在清醒犬引發(fā)的類過敏反應(yīng)情況。方法：分別經(jīng)靜脈滴注以120mL·h-1的給藥速度給予犬不同濃度的清開靈注射液和葛根素注射液,采用Dataquest A.R.T.4.3系統(tǒng)連續(xù)監(jiān)測(cè)給藥過程中及給藥后Beagle犬血壓和心率的變化并觀察犬的體征變化。結(jié)果：1.2mL·kg-1,2.3mL·kg-1,11.5mL·kg-1清開靈注射液對(duì)犬血壓和心率均未產(chǎn)生明顯的影響,Beagle犬也未出現(xiàn)明顯的體征變化；0.24mL·kg-1葛根素注射液對(duì)犬血壓和心率的影響不明顯,而0.47mL·kg-1葛根素注射液引起犬血壓明顯降低,平均動(dòng)脈壓在藥后30min時(shí)從藥前的(115.35±7.73)mmHg降低到(91.74±10.18) mmHg (n=4, P0.01),收縮壓從藥前的(147.33±14.65)mmHg降低到(112.88±6.51) mmHg (n=4, P0.01),但未見明顯的體征變化,心率變化也不明顯。結(jié)論：120mL·h-1的給藥速度下清開靈注射液未引起清醒Beagle犬發(fā)生類過敏癥狀；葛根素注射液可使清醒犬的血壓降低,并與劑量相關(guān)。 3利用犬PBMC評(píng)價(jià)清開靈注射液和葛根素注射液對(duì)細(xì)胞因子的影響及類過敏反應(yīng)與細(xì)胞因子的關(guān)系 目的：初步探究清開靈注射液和葛根素注射液對(duì)Beagle犬細(xì)胞因子的影響,研究類過敏反應(yīng)與細(xì)胞因子之間的關(guān)系。方法：通過梯度密度離心法分離犬PBMC,分別與類過敏陽(yáng)性藥Compound48/80及Tween80、清開靈注射液、葛根素注射液充分進(jìn)行反應(yīng)后利用相應(yīng)的犬細(xì)胞因子ELISA試劑盒測(cè)定PBMC釋放的細(xì)胞因子水平,主要測(cè)定的細(xì)胞因子為IFN-γ、TNF-α、IL-6。結(jié)果：Compound48/80與Tween80使PBMC分泌的TNF-α水平下降,清開靈注射液組和葛根素注射液組的TNF-α水平也出現(xiàn)了明顯的下降,且具有統(tǒng)計(jì)學(xué)意義上的顯著性差異PBMC與各組藥物反應(yīng)后分泌的IFN-γ水平有不同程度的下降,其中清開靈注射液引起的下降最為明顯。對(duì)IL-6的濃度進(jìn)行檢測(cè),檢測(cè)結(jié)果顯示各組的吸光度值均小于標(biāo)準(zhǔn)對(duì)照組的最小值,因此所測(cè)結(jié)果無意義。結(jié)論：Compound48/80, Tween80以及清開靈注射液和葛根素注射液可引起犬細(xì)胞因子IFN-γ、 TNF-α的分泌量減少。
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R725.9
本文編號(hào)：2434057
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R725.9
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