PURPOSE: The degradation of the extracellular matrix has been shown to play an important role in the treatment of hepatic cirrhosis. In this study, the effect of thalidomide on the degradation of extracellular matrix was evaluated in a rat model of hepatic cirrhosis. MATERIALS AND METHODS: Cirrhosis was induced in Wistar rats by intraperitoneal injection of carbon tetrachloride (CCl4) three times weekly for 8 weeks. Then CCl4 was discontinued and thalidomide (100 mg/kg) or its vehicle was administered daily by gavage for 6 weeks. Serum hyaluronic acid, laminin, procollagen type III, and collagen type IV were examined by using a radioimmunoassay. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and alpha-smooth muscle actin (alpha-SMA) protein in the liver, transforming growth factor beta1 (TGF-beta1) protein in cytoplasm by using immunohistochemistry and Western blot analysis, and MMP-13, TIMP-1, and TGF-beta1 mRNA levels in the liver were studied using reverse transcriptase polymerase chain reaction. RESULTS: Liver histopathology was significantly better in rats given thalidomide than in the untreated model group. The levels of TIMP-1 and TGF-beta1 mRNA and protein expressions were decreased significantly and MMP-13 mRNA and protein in the liver were significantly elevated in the thalidomide-treated group. CONCLUSION: Thalidomide may exert its effects on the regulation of MMP-13 and TIMP-1 via inhibition of the TGF-beta1 signaling pathway, which enhances the degradation of extracellular matrix and accelerates the regression of hepatic cirrhosis in rats.
Actins ; Animals ; Carbon Tetrachloride/toxicity ; Collagen Type III/metabolism ; Down-Regulation ; Extracellular Matrix/metabolism ; Immunohistochemistry ; Immunosuppressive Agents/*pharmacology ; Liver Cirrhosis, Experimental/chemically induced/*metabolism/pathology/*prevention & control ; Male ; RNA, Messenger/analysis/metabolism ; Rats ; Rats, Wistar ; Thalidomide/*pharmacology ; Tissue Inhibitor of Metalloproteinase-1/biosynthesis/*drug effects ; Transcription Factor RelA/biosynthesis/drug effects ; Transforming Growth Factor beta1/biosynthesis/*drug effects ; Transforming Growth Factors/metabolism

Objective:To investigate the effect of the lactitol powder combined with piperacillin sodium and tazobactam sodium in patients with spontaneous bacterial peritonitis (SBP), and the influence on the body microenvironment.Methods:The clinical data of 135 patients with SBP from January 2017 to December 2019 in Huxi Hospital Affiliated Jining Medical College were retrospectively analyzed. Among them, 68 patients were treated with lactitol powder combined with piperacillin sodium and tazobactam sodium (observation group), 67 patients were treated with piperacillin sodium and tazobactam sodium (control group). The curative effect was compared between 2 groups. The recovery time of clinical symptoms and signs (disappearance time of abdominal pain, disappearance time of abdominal distension, disappearance time of abdominal tenderness, recovery time of body temperature and recovery time of ascites white blood cell), liver function indexes (alanine aminotransferase, ALT; total bilirubin; albumin; aspartate aminotransferase, AST), microcirculation indexes (haptoglobin; procalcitonin; interleukin-6, IL-6; neutrophil gelatinase-associated lipocalin, NGAL), intestinal mucosal permeability indexes (endotoxin, blood ammonia, diamine oxidase) and adverse reactions (diarrhea, nausea and skin itching) were recorded.Results:The total effective rate in observation group was significantly higher than that in control group: 95.59% (65/68) vs. 82.09% (55/67), and there was statistical difference ( P<0.05). The disappearance time of abdominal pain, disappearance time of abdominal distension, disappearance time of abdominal tenderness, recovery time of body temperature and recovery time of ascites white blood cell in observation group were significantly shorter than those in control group: (6.15±1.34) d vs. (8.26±1.19) d, (5.34±1.29) d vs. (7.18±1.35) d, (7.59±1.65) d vs. (9.86±1.80) d, (5.28±1.20) d vs. (6.39±1.12) d and (10.87±2.25) d vs. (12.18±1.67) d, and there were statistical differences ( P<0.01). The ALT, total bilirubin, AST, haptoglobin, procalcitonin, IL-6, NGAL, endotoxin, blood ammonia and diamine oxidase 1 and 2 weeks after treatment in observation group were significantly lower than those in control group, and there were statistical differences ( P<0.01); there was no statistical difference in albumin between 2 groups ( P>0.05). There was no statistical difference in incidence of adverse reactions between2 groups ( P>0.05). Conclusions:The lactitol powder combined with piperacillin sodium and tazobactam sodium for SBP patients can more significantly improve the liver function and intestinal mucosal permeability, and promote the body microenvironment and the recovery of symptoms.