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Objective To investigate the therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride (CCl 4 )-induced liver fibrosis and its mechanism of action. Methods A total of 24 male C57BL/6 mice were randomly divided into normal group, model group, and Taohong Siwu decoction group, with 8 mice in each group. The mice in the model group and the Taohong Siwu decoction group were given intraperitoneal injection of 10% CCl 4 , and Taohong Siwu decoction was given by gavage since week 3 for 4 consecutive weeks. Liver function [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] was measured, and liver pathomorphology was observed. Real-time PCR was used to measure the mRNA expression of α-smooth muscle actin (α-SMA), hyaluronic acid synthase-2 (HAS-2), and collagen type Ⅰ(Col1), and Western blotting was used to measure the protein expression of α-SMA, Col1, and HAS-2. Primary hepatic stellate cells (HSCs) were isolated, and HAS-2 was silenced by siRNA to observe its influence on HSC activation. The t -test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the SNK or least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the model group had significant increases in serum liver function parameters (ALT, AST) and the Taohong Siwu decoction group had significant reductions in the serum levels of ALT and AST (all P < 0.01). Pathological staining showed that the model group had marked inflammatory cell infiltration and formation of fibrous septa by proliferated collagen fibers, and the Taohong Siwu decoction group had loose fibrous septa and alleviated inflammatory cell infiltration. Compared with the model group, the Taohong Siwu decoction group had significant reductions in the mRNA and protein expression of α-SMA and Col1(all P < 0.001). Compared with the normal group, the model group had a significant increase in the mRNA expression level of HAS-2 in liver tissue ( t =6.14, P < 0.05), and compared with the model group, the Taohong Siwu decoction group had a significant reduction in the protein expression level of HAS-2 (0.29±0.10 vs 1.00±0.12, t =70.73, P < 0.001). After HAS-2 was silenced by siRNA, the Si HAS-2+transforming growth factor β (TGFβ) group (treated with TGFβ) had significant reductions in the mRNA expression levels of α-SMA and Col-Ⅰ compared with the NC+TGFβ group ( P < 0.01). Conclusion Taohong Siwu decoction exerts a marked therapeutic effect on CCl 4 -induced liver fibrosis in mice by inhibiting HAS-2.
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Objective@#To compare the diagnostic efficacy of transient elastography (TE) FibroScan and acoustic radiation force impulse imaging (ARFI) combined with serological models including aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis-4 (FIB-4) in hepatitis B virus-related fibrosis.@*Methods@#Sixty-seven patients with chronic HBV infection from October 2014 to May 2017 in Department of Infectious Diseases, Putuo Hospital were enrolled. Both FibroScan and ARFI were conducted in all patients together with serological tests. According to the golden standard of pathology results, the diagnosis values of FibroScan, ARFI combined with APRI or FIB-4 were compared as noninvasive assessment for liver fibrosis. Data with homogeneity of variance were tested by t test, and data with heterogeneity of variance were tested by Mann-Whitney U test.@*Results@#Based on the pathology results, the receiver operating characteristic (ROC) areas under the curve (AUC) of APRI, FIB-4, FibroScan and ARFI in diagnosis of hepatic fibrosis ≥S2 were 0.752, 0.612, 0.885, and 0.850, respectively. The AUC of ROC curve in diagnosis of hepatic fibrosis ≥S3 were 0.746, 0.733, 0.851, and 0.863, respectively. The AUC of ROC curve in diagnosis of hepatic fibrosis ≥S4 were 0.782, 0.705, 0.962 and 0.981, respectively. Combined liver imaging technique and serological tests, such as APRI with FibroScan, APRI with ARFI, FIB-4 with FibroScan or FIB-4 with ARFI, the AUC of ROC curve in the 4 groups in diagnosis of hepatic fibrosis ≥S2 were 0.887, 0.861, 0.893, and 0.853, respectively; in the diagnosis of hepatic fibrosis ≥S3 were 0.873, 0.871, 0.900, and 0.875, respectively; and in diagnosis of hepatic fibrosis ≥S4 were 0.952, 0.981, 0.969, and 0.981, respectively. FibroScan and ARFI were positively correlated with liver inflammation (r=0.467, P=0.000; r=0.371, P=0.002) and jaundice (r=0.424, P=0.000; r=0.0.312, P=0.01), while negatively correlated with platelet (r=-0.331, P=0.006; r=-0.312, P=0.01). The AUC of ROC curve of FibroScan, ARFI and their combination with serological model were significantly increased compared with the single serological model (all P<0.05).@*Conclusions@#Serological models such as APRI and FIB-4 as well as liver imaging techniques such as FibroScan and ARFI are all valuable in assessment of hepatic fibrosis, while FibroScan and ARFI have better diagnostic value. ARFI is convenient to application for its integration with the ordinary ultrasound system. The sensitivity and specificity for diagnosis of hepatic fibrosis could be improved by combining serological model with FibroScan or ARFI. Combination of APRI and ARFI show the highest accuracy in diagnosis of hepatic fibrosis. Combination of serological models and transient elastic liver imaging is recommended for assessment and follow-up of HBV-related fibrosis.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy of Fuzhenghuayu capsule for the prevention of oesophageal variceal bleeding in patients with liver cirrhosis.</p><p><b>METHODS</b>A multicentre randomized placebo-controlled trial was conducted. A total of 181 liver cirrhosis patients were enrolled in the study and randomly assigned to different groups according to the level of oesophageal variceal bleeding. Patients with light oesophageal varices received Fuzhenghuayu capsule or a placebo. Patients with medium to heavy oesophageal varices received either Fuzhenghuayu capsule alone, Fuzhenghuayu capsule plus propranolol, or propranolol plus a placebo. Patients with a history of oesophageal variceal bleeding received either Fuzhenghuayu capsule plus propranolol, propranolol alone, or a placebo. For all patients, the treatment lasted 2 years. The primary end point of the study was oesophageal variceal bleeding. The secondary end points were liver cancer, death by any cause, and liver transplantation. Risk of bleeding and survival were statistically assessed.</p><p><b>RESULTS</b>The median follow-up time was 50 months. The patients with small oesophageal varices who were treated with Fuzhenghuayu capsule showed a significantly higher cumulative probability of bleeding than their counterparts treated with the placebo (3.4% vs. 23.7%, x² = 4.829, P =0.028). The patients with medium to heavy oesophageal varices and no history of oesophageal variceal bleeding who were treated with Fuzhenghuayu capsule plus propranolol showed a remarkably higher cumulative probability of bleeding than their counterparts treated with propranolol alone (15.2% vs. 43.6%, x² =6.166, P =0.013). There were no significant differences between the patients treated with Fuzhenghuayu capsule alone and those treated with propranolol alone (P =0.147) or the patients treated with Fuzhenghuayu capsule plus propranolol and those treated with Fuzhenghuayu capsule alone (P =0.147). The patients with history of oesophageal variceal bleeding who were treated with Fuzhenghuayu capsule showed significantly higher cumulative probability of bleeding and median time of bleeding than their counterparts treated with propranolol alone (44.0% vs. 24.2% and 40.00 ± 17.92 months vs. 7.00 ± 2.35 months; x² = 4.433, P =0.035). There were no significant differences in the cumulative probability of liver cancer and survival among all of the groups.</p><p><b>CONCLUSION</b>Fuzhenghuayu capsule can decrease the cumulative probability of bleeding in cirrhotic patients with light oesophageal varices. For cirrhosis patients with a history of oesophageal variceal bleeding, the combination of Fuzhenghuayu capsule plus propranolol can decrease the cumulative probability of bleeding with median or heavy varices.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Double-Blind Method , Drugs, Chinese Herbal , Therapeutic Uses , Esophageal and Gastric Varices , Gastrointestinal Hemorrhage , Liver Cirrhosis , Drug Therapy , Phytotherapy , Prospective Studies , Treatment OutcomeABSTRACT
Transforming growth factor-?(TGF-?) is a multifunctional growth factor. It plays a very important role in the growth, dif ferentiation, migration, apoptosis of cells and production of extracellular matr ix throughout many signaling pathways. MAPK cascade is one of those signaling pa thways. TGF-? can activate MAPKs and fulfill its multiple regulation on a varie ty of cells.