Exploration Of The Adverse Reaction Mechanism Induced By Chlorogenic Acid And Its Compound Injection

TCM injections, adverse reaction is a huge obstacle of the development of chinese medicine injection, which is the process of modernization of the TCM. TCM injection adverse reaction has many factors, in which, ingredient drug jurisprudence factors mainly concentrated in the CGA. The direction of the major studies of CGA is the sensitization it brings about. However, the diversity of the adverse characteristics of TCM injection, as well as clinical observation find out that in most cases of TCM ADR is organ injury. This study we suppose that the injection of CGA can damage organ and lead to systemic inflammatory response (SIRS) and multiple organ failure (MODS). Explore the toxicological effects of CGA and the corresponding injection.This thesis is composed by the literature review and experimental study.The first literature review analysis of the research status and main characteristics of the adverse reactions of TCM injections, the pharmacological effects of the focus of discourse of the hot subjects of CGA, as well as TCM injection adverse factors research results and characteristics about CGA. In the second literature review I mainly discuss the development and recent study of SIRS and MODS, Listing some of the experimental approaches of SIRS and MODS. These tow literature reviews provide ideas and innovation thoughts for the following experimental research.The name of experimental part is:CGA induced rat cytokines change which is the pathology basic of MODS and the observation of the damage to lung tissue. The experiment is consisted of two parts:The first part explore the CGA and the injection contented CGA affect the concentration of TNF-? and IL-10in the blood of rats. Intraperitoneal injection of TCM injection and CGA injection to the health male wistar rats as the method to make the adverse reactions animal models. Animals divided into normal saline, CGA low-dose group, Qing Kai Ling injection group. CGA high-dose group, Shuang Huang Lian injection group. Experiment time last7days and14days. After the days of injection levels of blood serum IL-10and TNF-a will be detected to explore the effects of CGA's and the injection's ability of the stimulation of these two factors, and by comparing the value the IL-10/TNF-?, we can find out the balance of inflammation-anti-inflammatory.The third part discusses the the lung injury in rats that CGA and TCM injection can do. Ntraperitoneal injection of TCM injection and CGA injection to the health male wistar rats as the method to make the adverse reactions animal models. Animals divided into normal saline, CGA low-dose group, Qing Kai Ling injection group, CGA high-dose group, Shuang Huang Lian injection group. Experiment time last7days and14days. After injectin myeloid peroxidase (MPO) activity in the lung tissue and catalase (CAT) activity in serum peroxide of the rats will be detected. We will also measure the water content of lung tissue and HE staining to evaluate the lung tissue damage.The experimental results:1Chlorogenic acid and serum caused by the injection of TNF-a and IL-10changes1.1Chlorogenic acid and injection-induced changes of serum TNF-aIn this study, we found that continuous infusion of low doses of CGA for14days, can be opened to the observed increased TNF-a. Equivalent of CGA measured Qing Kai Ling Injection for7days reduced the serum content of TNF-a, but increasre TNF-a content in14days. The reason for this phenomenon may be:the Qing Kai Ling Injection has strong anti-inflammatory effects; numerous clinical and experimental literatures show that in the early inflammation Qing Kai Ling injection can significantly reduce the efficacy of TNF-a [2]. Qing Kai Ling injection is composed of more than50kinds of substances. Led to this phenomenon may be the complexity of its composition.Continuous infusion of high doses of CGA and the same dose of CGA in Shuang Huang Lian injection7days reduce of TNF-a, but14days increased TNF-a, and among the three groups there are no significant differences. Instructions in changing scrum TNF-a concentrations. high doses of green acid, Qing Kai Ling Injection Shuanghuanglian injection have similar pharmacological effects.In14days group, the effect of elevated TNF-a is different between groups, indicating that after a long time injection of CGA can improve the ability of TNF-a content in serum in both experimental designed CGA concentration.1.2CGA and the injections cause the IL-10changes in serumIt was found that, compared with saline group, using low doses of CGA for7days, the concentration of IL-10has changed a little, while the Qing Kai Ling inhibited the IL-10. Low-dose of CGA after14days of administration increased the level of IL-10, Qing Kai Ling injection on the role of IL-10is not obvious. The reason for this phenomenon might be:the Qing Kai Ling injection components have interaction with CGA which led the pharmacological effects, zoom in or out. Speculate that CGA may be a major component of the change of Serum IL-10concentration Qing Kai Ling injection, because the two groups showed the same trend.Compared with the saline group, after injection of the CGA in high doses for7days, IL-10change is not obvious, But Shuang Huang Lian injection blocked IL-10.14days after administration of CGA the high-dose group showed the inhibition of IL-10. Shuang Huang Lian injection can increase the concentration of IL-10.7and14days, two points in time showed the different results. The reason for this phenomenon might be:the other ingredients in the CGA and Shuang Huang Lian injection interaction, leading to its pharmacological effects and the overall injection showed a different effect.CGA in low doses and hight does have no obvious difference in7days. But in14days they showed the opposite effect, CGA low dose to improve but high dose to inhibit.1.3CGA and the injection cause serum IL-10/TNF-a ratio changesIn this study, we found that low doses of CGA did not much impact to the serum IL-10/TNF-a ratio, while the Qing Kai Ling injection show that in7days increasing and14days reducing phenomenon, both the inconsistency may be due to the complex composition in the injection, the same but the change in the trend of the two relatively normal saline group, show that CGA may be an important factor of the change of the IL-10/TNF-?.High doses CGA and Shuang Huang Lian injection reduce the ratio of IL-10/TNF-a in7days but increased in14days. This also means that CGA is an important factor in Shuang Huang Lian injection on the changes of IL-10/TNF-?, Except the low dose group of the CGA, the other three groups have impact the ratio of IL-10/TNF-?, indicating that the Qingkailing, Shuanghuanglian and high-dose CGA can break the inflammatory-anti-inflammatory balance, which is in7days the three raised anti-inflammatory response, in14days the three improve the inflammatory response.2The observation of chlorogenic acid and injection damage in rat lung tissue2.1CGA and the injection change the myeloperoxidase activity in lung tissueIn this study, after using CGA and the injection, the7days the group of experimental lung tissue MPO activity compared with the saline group was not statistically significant. In the groups of14days, high-dose CGA group and Shuang Huang Lian group can observe the obvious increase of MPO activity. High doses of CGA and Shuang Huang Lian injection in long-term use can promote neutrophil infiltration of the lung tissue of rats, the release of MPO may produce a variety of oxidants and oxygen free radicals cause damage to the lung.2.2The impact of the catalase activity of CGA and injection in serumAfter7days of injection, the high doses of CGA can increase the serum levels of CAT activity, indicating that high doses of CGA in the continuous injection after a week can increase the antioxidant capacity of rat, low doses of CGA in7days injection has been seen to improv antioxidant capacity in rats. Shuang Huang Lian group and Qing Kai Ling group did not find any differences. After14days of injection, low doses of CGA, high doses of CGA and Shuang Huang Lian group found that CAT activity was reduced, the CGA and the Shuang Huang Lian can inhibit the activity of CAT, reduced antioxidant capacity. That may be another reason for the lung tissues oxidative damage.2.3chlorogenic acid and injection of rat lung tissue water contentIn the experiment of dry and wet ratio of lung tissue, we found that alter7days of administration there is no impaction on water content of lung tissue of all groups. But after14days of administration CGA, low-dose group and high dose groups and Shuang Huang Lian group are significantly higher than saline control group. Qingkailing group has no significant difference with the saline group, but has the tendency of increasing. Two consecutive weeks after administration of each set of experiments lung tissue can be edema.Conclusion:1High doses of CGA, Qing Kai Ling Injection and Shuang Huang Lian injection enables the body to produce TNF-a decreased after7days of use and then increased after14days of use. Low doses of CGA in the14days can increase TNF-?. TNF-? is an important cytokines of Inflammation. Overexpression of TNF-a will deal great damage to body organ. In the latter experiment we find out that after14days of using CGA lung tissue is found damaged which is Conformed the TNF-? overexpression in14days2Four groups showed their role of affect IL-10is significantly different, this may due to three reasons:First, the injection is a complex composition of many conpounds. Second, the IL-10is a compensatory factor of the inflammatory response to keep balance, its activation time and the length of time of maintaining the concentration is related to the environment. Third, CGA may be not a direct cytokine function as activation or inhibition of the IL-10, but indirectly by changing other factors which have an impact on IL-10. Therefore may be is the complx interaction of the cytokines lead to the phenomenon.3By observing the IL-10/TNF-a we found that except the low dose of CGA the other three groups have led to the imbalance of inflammatory-anti-inflammatory response of rats, which could lay the foundation for the further occurrence of MODS. Some paper reported that increased mortality in patients When IL-10/TNF-a is in a high ratio. In this experiment this phenomenon was not observed. That may be due to the experimental environment is sterile that we can not observe the symptom when immunosuppression happened in7days. This part of the study need to be further deepened.4CGA. directly or indirectly by increasing the nuclear translocation factor ?B expression to start the inflammatory cascade and cause tissue injury. Its first involving to the lung tissue.5CGA, Qing Kai Ling and Shuang Huang Lian injection could damage the lung tissue by activated neutrophils, and inhibition of CAT activity.