ABSTRACT
Objective: To study the protective effect of Eucommia ulmoides polysaccharide (EUP) on liver-fibrosis rats and investigate its mechanism. Methods: Models of liver-fibrosis rats induced by carbon tetrachlotide (CCl 4) were established by sc injection of pure CCl4 (5 mL/kg) and then peanut oil with 40% CCl4 (3 mL/kg) to the back of rats for eight weeks. After the models were ig administrated by EUP for eight weeks, the indexes of the liver and spleen in liver-fibrosis rats were calculated; ALT and AST activities and contents of TP and ALB in serum were examined; Meanwhile, the ratio between ALB and GLOB (AJG) was computed; The four levels of HA, LN, PCIII, and IV-C in serum of liver-fibrosis rats were determined. SOD activities and Hyp, MDA, and GSH-Px levels in liver tissue were examined; The expression of transforming growth factor-β1 (TGF-β1) in liver was observed. Results: EUP could obviously be against the index increasing of the liver and spleen (P<0.01) in liver-fibrosis rats induced by CCl4; remarkably inhibit the increasing of ALT and AST activities in serum (P<0.01); decrease the content of HA, LN, PCIII, IV-C, and GLOB in serum (P<0.01); increase the content of TP and ALB, and ratio of A/G in serum (P<0.01); decrease the MDA amd Hyp levels in liver tissue (P<0.01); and improve SOD activities and GSH-Px levels in liver tissue (P<0.01); and decrease the expression of TGF-β1 as well. The best effect of EUP was observed in the high-dose group and inhibition of EUP on fibrosis was in a dose-dependent manner. Conclusion: EUP has the remarkable protective effects on liver-fibrosis rats.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between mTOR signaling pathway and ALK-positive lymphoid cell lines.</p><p><b>METHODS</b>The expression of the downstream effector proteins of mTOR were analyzed by Western blot before and after Karpas299, BaF3/NPM-ALK and BaF3 cell lines treated with rapamycin. Effect of rapamycin on cell proliferation was detected by MTT assay. FACS was used to analyze apoptosis and cell cycles.</p><p><b>RESULTS</b>mTOR signaling phosphoproteins, p-p70S6K and p-4E-BP1 were highly expressed in ALK(+) Karpas299, BaF3/NPM-ALK and parental BaF3 cell lines, and they were dephosphorylated after 1 h withdrawal of IL-3 in BaF3 cells. After 48 h exposure to 10 nmol/L rapamycin, p-p70S6K and p-4E-BP1 proteins expression were decreased, and mainly for the former. The relative inhibitory rate to its control cells was 24.4% in Karpas299, 37.8% in BaF3/NPM-ALK and 61.6% in BaF3. The apoptotic ratio was increased from (11.97 +/- 0.11)% to (15.87 +/- 0.62)% in Karpas299 (P < 0.05), from (3.23 +/- 0.11)% to (7.67 +/- 0.49)% in BaF3 (P < 0.05) and from (1.90 +/- 0.47)% to (2.80 +/- 0.27)% in BaF3/NPM-ALK (P > 0.05). The fraction of G(1) phase cells increased from (37.63 +/- 1.91)% to (69.77 +/- 5.44)% in BaF3/NPM-ALK, from (31.13 +/- 2.51)% to (40.70 +/- 1.47)% in Karpas299 and (53.57 +/- 2.22)% to (63.70 +/- 1.20)% in BaF3 (P < 0.05).</p><p><b>CONCLUSION</b>NPM-ALK kinase can activate mTOR signaling pathway. Rapamycin can inhibit the proliferation of ALK(+) lymphoid cells by blocking mTOR signaling pathway and inducing cell cycling arrest at G(1) phase.</p>