幻灯片 1

Size: px

Start display at page:

Download "幻灯片 1"

肖冉
7 years ago
Views:

2 The galectin-3 serum level is correlated with prognosis of acute on chronic liver failure Yong-Feng Yang, M.D. The second hospital of Nanjing, affiliated to Southeast University

3 Background Insufficient hepatic tissue regeneration is one major reason for poor prognosis in liver failure patients. Galectin-3 (Gal-3), one of β- galactoside-binding proteins, its biological function including: cell adhesion regulation Cell chemotaxis and cell activation regulation Cell growth and cell apoptosis regulation Binding to AGEs(advanced glycosylation end products modified proteins), leading to changes in expression levels of some proteins.

4 Background Basic research shows that Gal-3 can promote proliferation of several types of cell, such as cornea cell, renal tubule cell and colonic epithelial cell. Animal experiments demonstrate that Gal-3 plays a hepato-protective role in animal models of ischemia / reperfusion injury and non alcoholic fatty liver. Clinical studies show that Gal-3 serum levels C of Child- Pugh C alcoholic cirrhosis patients is significantly higher than that of Child-Pugh A alcoholic cirrhosis patients, indicating that Gal-3 levels increased in patients with severe liver injury. The role of Gal-3 in liver failure is not clear.

5 Methods Hospitalized patients in liver disease department of the second hospital of nanjing from Jan 2014 to Dec patients with acute on chronic liver failure (ACLF) caused by HBV 38 patients with severe degree chronic hepatitis B. (TBIL 171.1ummol/L and PTA>40%) 26 patients with mild or moderate degree chronic hepatitis B 25 healthy persons as control.

6 Methods Treatment protocols: all the ACLF patients received combined treatment including nutritional support therapy, hepatoprotective agent therapy, symptomatic treatment, artificial liver support system if necessary. The baseline data, include serum biochemical tests, coagulation function test, serum galectin-3 levels (by ELISA method), symptoms, signs and complications were recorded. Follow up: every patients in ACLF group follow up for six months. Statistical analysis: Continuous variables were analyzed using independent Student s t-test. Mann-Whitney U test were used to analyze non normal distribution data. Logistic regression analysis were used to analyze risk factor correlated with prgnosis.

7 Figure 1. Galectin-3 serum levels at baseline in the four groups

9 Figure 2. Baseline galectin-3 serum levels of patients with death or survival prognosis in ACLF group.

11 Summarization The serum Galectin-3 level of ACLF patients was significantly higher than that of normal persons and chronic hepatitis B patients. The serum Galectin-3 level is correlated with prognosis of ACLF, patients with higher Gal-3 levels with better prognosis. Upregulation of Galectin-3 acting as protective factor in ACFL.

12 Figure 3. WNT/β-catenin signalling. (a), In the absence of active WNT β-catenin is degraded, and prospective target genes are in a repressed state. (b) If WNT signalling is active, β-catenin degradation is reduced. As β- catenin accumulates, it enters the nucleus, binds to T-cell factor (TCF)- and lymphoid enhancerbinding protein (LEF)-family transcription factors and activates transcription. The components shown are described in more detail in the text; additional pathway components are described on web sites that are linked to the main text. APC, adenomatous polyposis coli; β-cat, β-catenin; CBP, CREB-binding protein; CK, casein kinase; DKK, Dickkopf; DSH, Dishevelled; GBP, GSK3-binding protein; GSK, glycogen synthase kinase; LRP, LDLreceptor-related protein; P, phosphorylation; sfrp, secreted Frizzled-related protein; TCF, T-cell factor.

13 Human Hepatocytes (HH) culture Grouping:Gal-3 SiRNA group, Gal-3 vector group, blank SiRNA or vector group, and blank control group To harvest cells at different time points To detect the fluorescence expression by fluorescence microscope and Gal-3 protein expression by western blot in HH The proliferation ability of HH was detected by CCK-8 method. The protein levels of axin, total β-catenin, active β-catenin, total GSK-3β, and active GSK-3β were detected by western blot method.

14 Figure 4. Fluorescence expression of different MOI gradient in SiRNA group

15 Figure 5. Fluorescence expression of different MOI gradient in vector group

16 Figure 6. Galectin-3 expression detected by western blot of the five group Note: A. Blank control; B. Blank SiRNA; C. Gal-3 SiRNA; D. blank vector; E. Gal-3 vector.

17 Absorbency h 48h 72h time vs Blank control time vs Gal-3 vetor time vs Blank vecotr time vs Gal-3 SiRNA time vs Blank SiRNA Figure 7. Cell proliferation ability detected by CCK8 method at different time points of the five group

18 Figure 8. Wnt/β-catenin pathway protein expression detected by western blot method of the five group Note: A. Blank control; B. Blank SiRNA; C. Gal-3 SiRNA; D. blank vector; E. Gal-3 vector.

19 Acxin GSK-3β p-gsk-3β p-β -catenin β -catenin Blank control Gal-3 vetor Blank vecotr Gal-3 SiRNA Blank SiRNA Figure 9. Effects of overexpression or down-regulation of Gal- 3 on Wnt/ beta -catenin pathway in HH cells

20 Coclusion The Galectin-3 serum level in was significantly increased in ACLF patients, and the level of elevation were related to prognosis, which may be the protective factor. Overexpression or downregulation of Galectin-3 can promote or inhabit HH cells proliferation, and activation of Wnt/ beta -catetin pathway may be the mechanism. Galectin-3 may affect the prognosis of ACLF by promoting the regeneration of liver tissue.

21 Thanks

标题

环球中医药 2016 年 5 月第 9 卷第 5 期摇 Global Traditional Chinese Medicine, May 2016,Vol 郾 9, No 郾 5 摇 557 两种电针对脊髓损伤 14 天后大鼠运动功能神经元及 MEK2 p 鄄 ERK1 表达的影响论著宋良玉摇吕威摇景泉凯摇莫雨