1.The expression of basic fibroblast growth factor and transforming growth factorβ1 in virus myocarditis in mice
Tailing LU ; Ming LU ; Yuncui LIU
Journal of Clinical Pediatrics 2014;(7):677-681
s:Objective To investigate the possible role of basic ifbroblast growth factor (bFGF) and transforming growth factorβ1 (TGF-β1) in mice with Coxsackie viral myocarditis and their relationship. Methods Eighty male BALB/c mice, 4 weeks old, were divided randomly into study group (n=40) and control group (n=40). The study group was repeated intraperitoneally injected with Coxasckie viral B3 to establish the model of viral myocarditis, while the control group was injected with virus-free Eagle’s medium in the same period. On the 7th, 14th, 28th and 42th day after the ifrst injection, 8 alive mice selected randomly from each group were sacriifced to examine the myocardial collagen volume fraction (CVF) by Masson dyeing, and to detect the protein and mRNA expression of bFGF and TGF-β1 by RT-PCR and immunohistochemistry. The correlations were analyzed. Results At each time point, the expressions of protein and mRNA of bFGF and TGF-β1 both in study group were signiifcantly higher than those in control group (P<0.01), and gradually increased over time. The expressions of protein and mRNA of bFGF and TGF-β1 were positively correlated with CVF (r=0.86~0.95, all P<0.01). In addition, the expressions of protein and mRNA of bFGF also had positive correlation with the expression of protein and mRNA of TGF-β1 (r=0.94, 0.92, P<0.01). Conclusion bFGF and TGF-β1 may promote the occurrence and development of myocardial ifbrosis in viral myocarditis, which may provide a new target for future treatment of myocardial ifbrosis.
2.Expression of bFGF and TGF-β1 in different stages of myocardial ifbrosis
Tailing LU ; Ming LU ; Yuyin CHANG
Journal of Clinical Pediatrics 2016;34(5):371-374
Objective To study the expression of basic ifbroblast grouth factor (bFGF) and transforming growth factorβ1 (TGF-β1) in different stages of myocardial ifbrosis (CFs). Methods CFs of neonatal Sprague-Dawley rats were isolated with the method of trypsin digestion and differential anchoring velocity, then cultured in vitro. The generation 2-4 of CFs were used for the experiment and randomly divided into 2 groups:the control group were cultured without AngII , and the test group were cultured with AngII 10-6 mol/L. The test group were cultured for 12, 24, 48, and 72 h respectively, and then the synthesis of col agen were measured by ELISA, the bFGF, TGF-β1-mRNA expression was measured by RT-PCR, and the bFGF and TGF-β1 protein expression was measured by western blot analyses. Results Compared with those of control group, the expressions of bFGF and TGF-β1 both in gene and in protein in the test groups increased gradual y with the timing (P?0.01). Correlation analysis found that the expression of bFGF mRNA and protein were positively associated with TGF-β1 mRNA and protein (r?=?0.967, 0.947, P?<0?.05), and both bFGF and TGF-β1 were positively associated with the supernatant col agen. (r?=?0.932, 0.881, 0.930, 0.896, P?<0?.05). Conclusion bFGF and TGF-β1 may be involved in the occurrence and development of myocardial ifbrosis.
3.Effect of Carvedilol on the expression of inflammatory factor in myocardial tissue of the mice with myocardial fibrosis induced by coxsachievirus B3
Yuncui LIU ; Ming LU ; Tailing LU ; Lingjian MENG
Chinese Journal of Applied Clinical Pediatrics 2014;29(18):1407-1412
Objective To study the role of transforming growth factor-β1 (TGF-β1),connective tissue growth factor (CTGF)and endothelin-1 (ET-1) in myocardial tissues of the mice with myocardial fibrosis induced by coxsachievirus B3 (CVB3) and the effect of Carvedilol intervention for it in acute stage and chronic phase of viral myocarditis.Methods Forty male BALB/c mice were randomly divided into 4 groups (10 cases in each group):control group,model group,Carvedilol acute phase intervention group,the chronic phase intervention group.Mice in model group and Carvedilol intervention groups were inoculated with CVB3 (100TCID50/0.1 mL) by peritoneal injection fortnightly.Mice in control group were given normal saline(NS) instead equivalently.Mice were poured Carvedilol (10 mg/kg per day for 2 weeks) from the second day in acute phase intervention group and from the fourth week in the chronic phase intervention group,while mice of control group and model group were poured with equivalent NS instead.At the end of 6 weeks,mice were sacrificed.Heart weight index (HWI) was determined.The collagen volume fraction (CVF) of left ventricular myocardial tissue were examined after Masson staining.Expressions of ET-1,TGF-β1 and CTGF were detected by enzyme linked immunosorbent assay and immunohistochemistry staining respectively; the mRNA expression was tested by reverse transcription-polymerase chain reaction.Results Compared with the control group,HWI and CVF of model group increased significantly(all P < 0.01),those of the intervention groups decreased than those of the model group(all P < 0.01),and in the acute phase those of the intervention group were significantly lower than those in chronic phase intervention group(all P < 0.05).The expressions of TGF-β1,CTGF,ET-1 and their mRNA in model group were increased significantly than those in the control group(all P <0.01),and were decreased in acute and the chronic phase intervention group than those in model group(all P <0.01),while those were significantly lower in acute phase intervention group than those in chronic phase intervention group (all P < 0.01).Conclusions TGF-β1,CTGF and ET-1 may be involved in myocardial fibrosis induced by CVB3.Compared with the chronic phase intervention,the acute phase intervention of Carvedilol can reduce myocardial fibrosis more efficiently by down-regulating the excessive expression of inflammatory factors.
4. Qualitative pathological assessment of liver fibrosis regression after antiviral therapy in patients with chronic hepatitis B
Yameng SUN ; Jialing ZHOU ; Lin WANG ; Xiaoning WU ; Yongpeng CHEN ; Hongxin PIAO ; Lungen LU ; Wei JIANG ; Youqing XU ; Bo FENG ; Yuemin NAN ; Wen XIE ; Guofeng CHEN ; Huanwei ZHENG ; Hai LI ; Huiguo DING ; Hui LIU ; Fudong LYU ; Chen SHAO ; Tailing WANG ; Xiaojuan OU ; Binqiong WANG ; Shuyan CHEN ; Hong YOU ; Jidong JIA
Chinese Journal of Hepatology 2017;25(11):819-826
Objective:
To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression.
Methods:
Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment.
Results:
A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (