ABSTRACT
Objective To explore the dynamic expressions and the significance of Notch/Jagged signal pathway in rat model of hepatic fibrosis. Methods A total of 42 healthy male SD rats were randomly divided into normal control group (n=6) and model group (n= 36). The model group was further divided into six subgroup according to different time points: subgroups of 4 days, 1, 2, 4, 6 and 8 weeks with six rats in each subgroup. The rat model of hepatic fibrosis was induced by dimethylnitrosamine (DMN). The serum levels of alanine aminotransferase (ALT), aspertate aminotransferase (AST), albumin (Alb) and hyaluronic acid (HA) were detected dynamically after 4 days, 1,2,4,6 and 8 weeks of injection. The liver tissues were observed under optical microscope after HE and Masson staining. Notch-1, Jagged-1 mRNA and protein in liver were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The comparison of means among groups was done by univariate ANOVA. Results The hepatic fibrosis model was successfully induced by DMN injection and pseudolobules were found after 4 weeks of injection. The serum levels of ALT, AST, Alb and HA were all increased after 4 day of injection and peaked at week 4 which were all significantly higher than those in control group (F=83.10, 104.63, 54.24, 203.81,respectively; all P＜0.05). The expressions of Notch-1, Jagged-1 mRNA and protein in model group were all significantly increased than those in control group (F=282. 44, 369.14, 374.17, 256. 14,respectively;P＜0. 01). And the expressions of Notch-1, Jagged-1 were closely correlated with the hepatic fibrosis stages and transforming growth factor β1 (TGFβ1) expression (r=0. 821, 0. 917,0. 767,0. 844, respectively; P＜0. 01 ). Conclusions The Notch/Jagged pathway may participate in the development of hepatic fibrosis, which is closely correlated with the progression and severity of liver fibrosis.
ABSTRACT
ObjectiveTo investigate the effects of exogenous transforming growth factor β1 on the apoptosis of nerve cells and its functions following spinal cord injury in rats.MethodsNinety-six male Wistar rats were randomly divided into 4 groups:group A(control group),group B(spinal cord injured group),group C (spinal cord injuried +TGF-β1 treated group),group D (spinal cord injuried +anti-TGF-β1 treated group).The rat model of spinal cord injury was found by the Allen's method.In group C and D,drugs were injected into subarachnoid cavity continuously by minipump.The changes of spinal cord were observed by HE staining.Nerve cells apoptosis was detected by transferase-medi-ated dUTP nick end labeling (TNUEL) method and the expression of cell apoptosis factor Fas by immunohistochemistry staining.Functional recovery of hind limbs was measured by Basso-Beattie-Bresnahan locomotor open field behavioral rating test.ResultsThe expression of TGF-β1and Fas increased following spinal cord injury.The amount of TGF-β1and Fas reached the peak 7days and 1day after injury.The apoptosis of neuron had increased and peaked 8 hours after injury.The apoptosis of neuroglia cells had increased and peaked 7 dayss after injury.The slight changes was found in spinal cord in group C.Both of the number of apoptosis of nerve cells and expression of the apoptosis factor (Fas) decreased significantly; compare with group B and D.The BBB score was higher in group C than that in group B and D.ConclusionTGF-β1 can improve the functional recovery of spinal cord by inhibiting the nerve cell apoptosis after the spinal cord injury.