RESUMO
In order to investigate whether Yinchenhao decoction (YCHD) attenuates hepatic fibrogenesis in the bile duct ligation (BDL) model via recovering and restoring the self-regulation and balance of the renin-angiotensin system (RAS), 33 specific-pathogen-free (SPF) male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows: G1, the sham group (n=4); G2, BDL 7-day group (n=5); G3, BDL+YCHD 430 mg/mL (n=8); G4, BDL+losartan 0.65 mg/mL (ARB group, n=8); G5, model group (BDL without any treatment, n=8). YCHD and losartan (10 mL·kg(-1)·day(-1)) were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respectively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IDBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological changes were observed by transmission electron microscopy (TEM) and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system (RAS) components including angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), ACE2, angiotensin II (AngII) as well as transforming growth factor β1 (TGFβ1). The experimental data were analyzed by principle component analytical method of pattern recognition. The results showed that biochemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group (P<0.05). Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups (P<0.05). Serum AST level in G3 was significantly lowered than in G5 group (P<0.05), but there was no significant difference in ALT among G3, G4 and G5 groups (P>0.05). Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression levels of ACE2, ACE, AngII, AT1R and TGFβ1 in G2, G3 and G4 groups were significantly higher than in sham group (P<0.05), and lower than in G5 group (P<0.05). However, the differences among G2, G3 and G4 groups were not significant (P>0.05). ACE2 protein expression in G3 group was significantly higher than in G2 group (P<0.05) and there was no significant difference in comparison with G4 group (P>0.05). Moreover, the protein expression of TGFβ1 in G3 group was significantly lower than in G5 and G4 groups (P<0.05). Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFβ1 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.
Assuntos
Animais , Masculino , Ratos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Química , Farmacologia , Regulação da Expressão Gênica , Fígado , Patologia , Cirrose Hepática , Metabolismo , Patologia , Testes de Função Hepática , Losartan , Ratos Sprague-Dawley , Sistema Renina-AngiotensinaRESUMO
<p><b>OBJECTIVE</b>To investigate the effects of Chinese kidney-tonifying drugs on bone mineral density, biomechanics, 25-hydroxy Vitamin D3 and 1,25-dihydroxy Vitamin D3 of ovariectomized osteoporosis rats, and explore the mechanism of treating osteoporosis with the drugs.</p><p><b>METHODS</b>Thirty-six female SD rats (four months) were randomly divided into model group, sham group and treatment group. All the rats had been ovariectomied except those in sham group. Selecting 4, 8, 12 weeks in the experiment, the value of bone mineral density (BMD) was measure by dual energy X-ray absorptiometry (DEXA) of femoral head, while the biomechanics machine was applied to analysis femoral head biomechanics index and ELISA method was used to detect the content of 25-hydroxy Vitamin D3 and 1,25-dihydroxy Vitamin D3 discern in blood-serum, liver and kidney.</p><p><b>RESULTS</b>Treatment group rats' BMD of femoral head was enhance compared with model group, significant differences were absent (P<0.05), and the maximal load and maximal stress measurement were improved, significant differences were absent (P<0.05). As the content of 25-hydroxy Vitamin D3 and 1,25-dihydroxy Vitamin D3 discern in blood-serum, liver and kidney were elevate, furthmore there were significant differences in group comparison, all significant differences were absent (P<0.05). But those compared with sham group, there was no significant difference (P>0.05).</p><p><b>CONCLUSION</b>In the early period in absence of estrogenic hormone, the Chinese kidney-tonifying drugs could activate bone metabolism to raise BMD and reinforce quality of bone through up-regulating expression of 25-hydroxy Vitamin D3 and 1,25-dihydroxy Vitamin D3 at protein level.</p>