| Background:Tripterygium wilfordii Hook.f.,also known as Tripterygium wilfordii,vegetable insect medicine,red medicine,water wild grass,is a kind of perennial vine,which comes from the geranium family of Tripterygium wilfordii and is widely distributed in southwest China.Tripterygium wilfordii is a kind of traditional Chinese medicine commonly used in Chinese traditional medicine.The earliest medicinal records of Tripterygium wilfordii appear in "South Yunnan".Its nature,taste and meridian efficacy are recorded as bitter taste,cold nature,great poison,heart meridian and liver meridian.It can dispel wind and dampness,promote blood circulation and dredge menstruation,relieve swelling and pain,eliminate parasites and detoxify.In clinic,Tripterygium wilfordii can treat inflammation-related and autoimmune diseases,including rheumatoid arthritis,renal transplant rejection,chronic urticaria,nephrotic syndrome,severe joint psoriasis,systemic lupus erythematosus,and other immune and inflammation-related diseases,and even in recent years,it has been found that Tript erygium wilfordii has good anti-tumor effect,including leukemia,pancreatic cancer and so on.Based on its rich biological activity and outstanding clinical therapeutic effect,Tripterygium wilfordii has been widely accepted by the world in recent decades.However,with the wide application of Tripterygium wilfordii preparation,its toxicity and side effects are becoming more and more prominent.many studies and clinical studies have confirmed that Tripterygium wilfordii preparation has clear multisystem to xicity of liver,kidney,spleen,gastrointestinal tract or other organs.its toxicity risk and its narrow treatment window seriously limit the clinical application of Tripterygium wilfordii preparation.The compatibility of traditional Chinese medicine,that is,the combined use of two or more kinds of traditional Chinese medicine,is the main form of traditional Chinese medicine,which can increase efficiency,reduce toxicity,expand the scope of treatment,adapt to complex changes of disease and prevent drug toxicity.In recent years,based on the basic theory of traditional Chinese medicine,the use of traditional Chinese medicine compatibility to restrict the toxicity of Tri pterygium wilfordii preparation has gradually become a hot spot,but the final results and related mechanisms are not clear.Objective:To better confirm the effect of compatibility of traditional Chinese medicine on reducing hepatotoxicity of Tripterygium wilfordii preparation,and to explore the possible mechanism of compatibility of traditional Chinese medicine in reducing hepato toxicity of Tripterygium wilfordii preparation.Methods:1.Systematically search China knowledge net database(CNKI),China biomedical lit erature database(CBM),Wanfang database(WanfangData),Chinese traditional m edicine periodical database(TCMOnline),PubMed database,screen the rat exper imental study on the compatibility of traditional Chinese medicine to reduce the he patotoxicity of Tripterygium wilfordii preparation,extract the changes of liver injury index ALT and AST before and after intervention,and analyze the reticular Meta with Stata software.2.The liver injury model of NIH mice was established,and the mice were given Rehmannia glutinosa water extract(high-dose group,low-dose group)or only Rehm annia water extract.After 21 days,the mice were killed,the levels of ALT,AST and ALP in serum were detected,the liver tissue sections were stained with HE,the expression of Nrf2 and NQO1 in liver was detected by immunohistoche mistry,and the expression of SOD,MDA and GSH-px in liver homogenate was detected by Elisa.The expression of total Nrf2,nuclear Nrf2 and cytoplasmic Nrf2 in liver homogenate was detected by WesternBlot,and the levels of Nrf2mRN A and NQOlmRNA were detected by RealtimePCR.Results:1.A total of 23 experimental studies were included in the systematic review for com prehensive analysis.The results of direct Meta analysis showed that the compatibility of traditional Chinese medicine could reduce the serum indexes of ALT(SMD=-1.67,95%CI-1.83,-1.51)and AST(SMD=-1.51,95%-1.66,-1.36)in rats with liver injury caused by Tripterygium wilfordii.Indirect reticular Meta analysis was used to analyze the compatibility of single traditional Chinese medicine.The results showed that the order of attenuated toxicity of single traditional Chinese medicine was as follows:Radix Rehmanniae>Radix Paeoniae Alba>Glycyrrhiza uralensis>Panax notoginseng>dodder>Astragalus>Qingfengteng.2.The animal experiment showed that compared with the control group,the pathology of TP model group showed hepatic cord disorder and large area watery degenera tion,some inflammatory cell infiltration,serum ALT and AST levels significantly increased,liver MDA levels significantly increased(P<0.05),GSH-px levels decre ased(P<0.05)and Nrf2 expression decreased(P<0.05).The expression levels of total Nrf2,nuclear Nrf2 and NQO1 were significantly decreased,and the relative e xpression of NQO1mRNA was significantly decreased(P<0.05).Compared with TP model group,TP+HRG group and TP+LRG group significantly decreased the levels of serum ALT(P<0.05)and AST(P<0.05),decreased the level of MDA(P<0.05),and increased the level of SOD(P<0.05),GSH-px(P<0.05)and the expr ession of Nrf2(P<0.05).Among them,the expression of total Nrf2(P<0.05),pla sma Nrf2(P<0.05)and NQO1(P<0.05),Nrf2(P<0.05)and NQO1mRNA(P<0.05)increased in TP+HRG group,and nuclear Nrf2(P<0.05)expression increased in TP+LRG group.But there was no significant difference in others(P>0.05).Conclusion:1.The compatibility of different traditional Chinese medicines can reduce the liver injury caused by Tripterygium wilfordii in rats,and Rehmannia glutinosa has the best effect.2.The water extract of Radix Rehmanniae can reduce the liver injury induced by trip tolide and reduce the level of oxidative stress in the liver.The mechanism may be related to the enhancement of the initiation of Nrf2 and the increase of the expression of downstream antioxidant NQO1. |
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