Efficacy of decoction from Jieduan Niwan formula on rat model of acute-on-chronic liver failure induced by porcine serumEnglish Full Text
Li Jinxia;Zhang Qiuyun;Gao Lianyin;Du Yuqiong;Chen Yu;Institute of Traditional Chinese Medicine Diagnosis, Hunan University of Chinese Medicine;Hunan Key Laboratory of Traditional Chinese Medicine Diagnosis;School of Traditional Chinese Medicine, Capital Medical University;Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research;Department of Artificial Liver, Beijing You An Hospital Affiliated to Capital Medical University;
Abstract: OBJECTIVE: To dynamically observe the efficacy of Jieduan Niwan formula（JDNW） on a rat model of acute-on-chronic liver failure（ACLF）.METHODS: Seventy Wistar rats were divided into control group（6 rats）, model group（22 rats）, JDNW group（21 rats）, and SP600125 group（21 rats）.13 weeks’ porcine serum injection followed with D-galactosamine and lipopolysaccharide joint acute attack was used to establish ACLF model.Rats in JDNW group were orally given JDNW formula for 3 days before acute attack; rats in SP600125 group were injected with SP600125 30 min ahead of acute attack. Rats were sacrificed respectively at4, 8 and 12 h after model established. Alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, total bilirubin（TBIL）, Creatinine（CR）, blood urea nitrogen（BUN）, prothrombin activity（PTA）were examined by biochemical process, Tumor necrosis factor-alpha（TNF-α）, interleukin-1β（IL-1β）,interleukin-6（IL-6）, interleukin-10（IL-10）, transformed growth factor-beta 1（TGF-β1）, High mobility group box-1（HMGB-1）, CD3, CD4, CD8 were analyzed by enzyme-linked immunosorbent assay, apoptotic index（AI） was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling staining, expression of Bad, phosphorylated Jun N-terminal kinases（p-JNK） and Cytochrome C（Cyt C） were detected by immunohistochemical analysis, Bax and Bid were detected by Western blot analysis.RESULTS: In model group, the levels of ALT, AST,TBIL, CR, BUN, IL-1β, IL-6, IL-10, TGF-β1 and HMGB-1 remarkably increased and PTA decreased compared with control group（P ＜ 0.05）, as time goes on, ALT, AST, TBIL, CR, BUN, continued to grow,while IL-1β, IL-6, IL-10, HMGB-1, TGF-β1 and PTA gradually decreased; massive necrosis could be seen; the levels of TNF-α, CD3, CD4, CD8, AI, p-JNK,Bax, Bad, Bid and Cyt C increased at 4 h and peaked at 8 h, but decreased at 12 h（P ＜ 0.05）. JDNW group, by contrast, showed less pathological injury,increased PTA level, and reduced ALT, AST, TBIL,TNF-α, IL-1β, IL-6, IL-10, TGF-β1, HMGB-1, CD3, CD4 and CD8 levels（P ＜ 0.05）, moreover, the AI and expression of p-JNK, Bax, Bad, Bid and Cyt C were lower than model group at 4 and 8 h but were higher at 12 h（P ＜ 0.05）. Similar results were observed in SP600125 group.CONCLUSION: An ACLF rat model with low mortality can be established by porcine serum joint with D-galactosamine + lipopolysaccharide induction;JDNW decoction can effectively suppress the inflammatory reaction, improve the immune system,and protect the liver of ACLF rats, the mechanism might involve the inhibition of the JNK-induced mitochondrial apoptotic pathway.
Keywords：
Acute-on-chronic liver failure; JNK mitogen-activated protein kinases; Apoptosis; Jieduan Niwan formula;
- DOI：
10.19852/j.cnki.jtcm.2020.04.009
- Series：
(E) Medicine ＆ Public Health
- Subject：
Traditional Chinese Medicinal Herbs
- Classification Code：
R285.5
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