RESUMO
The study employed a rat model to examine the effects of taurine (Tau) on prevention and therapy of non-alcoholic fatty liver disease (NAFLD). In model rats maintained on a high-fat diet (HFD), the serum levels of ALT, AST, triglycerides, cholesterol, and LDL were higher than the corresponding levels in normal control and NP groups (p<0.05). In Tau-prevention and Tau-treatment groups, the serum levels of AST and triglycerides were lower than in HFD rats (p<0.05). In HFD rats, diffuse fatty degeneration and infiltration with inflammatory cells was observed in the liver; in the ileal mucosa, the villi were fractured or absent, the epithelium was exfoliated and infiltrated with inflammatory cells. The levels of TGF-ß, IL-9, and their mRNA in the liver and ileal mucosa of HFD rats were significantly higher than in normal control and NP groups (p<0.05). In Tau-prevention and Tau-treatment groups, these levels were significantly lower than in HFD rats (p<0.05). Thus, TGF-ß and IL-9 can be implicated in NAFLD genesis, while Tau can preventively or therapeutically diminish the damage to the liver and ileal mucosa in rats with this disease by down-regulating the expression of TGF-ß and IL-9.
Assuntos
Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica , Taurina/farmacologia , Animais , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Interleucina-9/genética , Interleucina-9/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Masculino , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Clusterin (CLU) is expressed in a wide variety of human tissues and fluids. Overexpression of cytoplasmic clusterin (sCLU) has been implicated in cancer development and progression. The aim of the present study is to evaluate the association of sCLU overexpression with clinicopathological features of human gastric carcinomas (GC).We constructed a gastric cancer tissue microarray containing 173 primary gastric carcinomas and 70 paired non-neoplastic mucosa specimens. The expression of sCLU was studied by immunohistochemistry. The correlations between sCLU expression and clinicopathological features, p53 abnormality, as well as Ki67 activation were analyzed. Overexpressions of sCLU was detected in 28.5% (n=165) of primary GCs by immunohistochemical staining, but not in non-neoplastic mucosa. Clinical association study found that overexpression of sCLU was significantly correlated with lymph-node metastasis (p < 0.001), tumor invasion (p < 0.001) and TNM stage (p < 0.001). In Kaplan-Meier survival analysis, overexpression of sCLU was significantly correlated with unfavorable survival in advanced GCs (p < 0.03). Furthermore, the association of sCLU with abnormal expression of p53 was ascertained. These results suggested that overexpression of sCLU was involved in the progression of GC and it's oncogenic function might be associated with p53 abnormality. Overexpression of sCLU seems to be related with patient's shorter survival in late stage GC.
