Study On Liver Injury Induced By Five Chinese And Western Medicine Compound Preparations In Mice

At present,the compound preparations of Chinese and western medicines are widely used in China,but due to their complex components,some problems have also occurred in the process of use.In recent years,the State Food and Drug Administration has continuously issued information reports on adverse reactions of Chinese and western medicine compound preparations,which was released on September 19,2010(Issue 32).Concerned about the safety of Chinese and western medicine compound preparations,VC Yinqiao Tablets;2013 Published on March 04(Issue 53)Concerned about the risks of using Chinese and Western medicine compound preparations Zhenju Jiangya Tablets;June 26,2015(Issue 67)"Concerned about the risks of Chinese and Western medicine compound preparations",informing Chinese and Western medicine Adverse reactions of the compound preparation Ganmaoqing tablets(capsules)and Naoluotong capsules;On October 19,2016,the "Adverse Drug Reaction Information Information Bulletin"(Issue 71)released "Concerns about thedrug use risk of the new compound Daqing leaf".In the above information on adverse drug reactions,the Chinese and western medicine compound preparations included VC Yinqiao Tablets,Ganmaoqing Tablets,Zhenju Antihypertensive Tablets,Xinfu Daqing Leaf and Naoluotong Capsules.Among them,the VC Yinqiao tablets,Ganmaoqing tablets and the new compound Daqing leaves all contained acetaminophen,and all of them suggested the risk of liver injury in the "Adverse Drug Reaction Information Notification".VC Yinqiao tablets: about 0.5g / tablet,containing 105 mg of acetaminophen;cold clear tablets: 0.22 g / tablet,containing12 mg of acetaminophen;new compound Daqing leaves: 0.32 g / tablet,containing paracetamol 75 mg of phenol.Paracetamol is currently the most widely used antipyretic and analgesic,but excessive use of this drug can cause liver cell toxicity and lead to liver damage.Purine receptors have many and complex biological effects,and play a very important role in the regulation of many diseases.Purine receptors are divided into Pl receptors(receptors for adenosine interactions)and P2 receptors(receptors for ATP and its analogs).P1 receptors are adenosine receptors(ARs).Adenosine receptors play a very important role in many organs and tissues in the body.ARs are widely present in hepatocytes and play a non-negligible role in the pathogenesis of liver disease.Previous research by this research group shows that adenosine A1 R and A2 AR participate in the process of paracetamol-induced liver injury.We speculate that the mechanism of liver injury caused by Chinese and western medicine compound preparations containing paracetamol may also be related to adenosine receptors.A search of related literatures revealed that the research on related Chinese and western medicine compound preparations mostly focused on its component analysis and quality control,and the research on its liver toxicity was relatively lacking.It is necessary to have a deeper understanding of the drug-induced liver injury caused by the related Chinese and Western medicine compound preparations and a deeper understanding of its liver toxicity,which is conducive to better determine the safe administration days in the application process of the related Chinese and Western medicine compound preparations.The study on the correlationbetween liver toxicity and administration days of related Chinese and western medicine compound preparations and the expression level of related receptors,in order to further explore the liver toxicity of related Chinese and western medicine compound preparations and its mechanism,the related receptors may become therapeutic related Chinese and western medicine compound preparations An effective potential therapeutic target for liver damage caused by To provide new ideas for the effective prevention and treatment of liver injury caused by related Chinese and western medicine compound preparations,it has broad prospects and important social value.OBJECTIVE: To investigate the effects and some mechanisms of three Chinese and western medicine compound preparations,such as VC Yinqiao Tablet,Ganmaoqing Tablet,and Xinfang Daqing Leaf,on the liver damage in mice.METHODS: 180 6-8 week-old Kunming mice were randomly divided into 6 groups of 30 mice each,which were blank group,Ganmaoqing tablet group,Naoluotong capsule group,VC Yinqiao tablet group,Xinfufang Daqing leaf Group and Zhenju antihypertensive tablet group.Except the blank group,the other groups were given a daily dose of 9.1 times the daily dose according to body weight.The blank group was given the same amount of normal saline,and each group was administered by single intragastric administration.On the 7th,15 th,and 30 th days after the administration,10 mice were randomly selected from each group,and the orbital blood was taken and the liver was removed by laparotomy after weighing.The body weight and liver weight of the mice were recorded.Serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(AKP),and total bile acid(TBA)levels were measured after blood treatment.The pathological changes of liver tissue were observed by HE staining.Serum index levels and pathological sections of liver tissues were selected.The administration group that may have significant liver damage was selected for further experiments.The Western Blot method was used to detect the liver injury in the administration group.The adenosine A1 receptor(A1R),A2 A receptor(A2AR)in liver tissues on the 7th,15 th and 30 th days after administrationWhat happened to the expression of HRP? Immunohistochemical method(ICH)observed the liver injury group and the blank group,compared the adenosine A1receptor(A1R),A2 A receptor(A2AR)Express the situation.RESULTS: Compared with the blank group,after the 7th,15 th,and 30 th days of administration of the Ganmaoqing tablet group,Naoluotong capsule group,and Zhenju Jiangya tablet group,the VC Yinqiao tablet group and the new compound Daqing leaf group After 7 days and 15 days of administration,there was no significant difference in the comparison of liver index;there was no significant difference in the serum levels of AST,ALT,AKP and TBA.And the liver tissue pathological sections were stained,and no obvious damage was found in the liver tissue.Compared with the blank group,the liver index of the VC Yinqiao tablet group after 30 days of administration and the new compound Daqing leaf after 30 days of administration showed statistically significant differences(P <0.05),and the expressions of AST,ALT,AKP,and TBA Significantly increased(P <0.05)and HE staining showed more obvious liver tissue damage.The expressions of adenosine A1receptor(A1R)and A2 A receptor(A2AR)in liver tissues of VC Yinqiao tablet group and new compound Daqing tablet group increased in sequence on the 7th,15 th and30th days of administration.Compared with the blank group,the expression levels of adenosine A1 receptor(A1R)and A2 A receptor(A2AR)in liver tissues of the Wei C Yinqiao tablet group and the new compound Daqing leaf group were significantly increased 30 days after administration(P <0.05).Conclusion: After 30 days of administration of the traditional Chinese and western medicine compound VC Yinqiao tablet group and the new compound Daqing leaf group,the liver of KM mice was significantly damaged.The damage may be related to the increased expression of adenosine A1 receptor(A1R)and A2 A receptor(A2AR)in liver tissue.