Objective:To investigate the effect and underlaying mechanism of aerobic exercise on aging-induced hepatic fi-brosis.Method:Thirty-two SPF grade C57BL/6J male mice were used,including 16 mice aged 2 months(young group)and 16 mice aged 19 months(senescent group).Both the aging group and the young group underwent one week of acclimatization.The animals were randomly divided into four groups:young control group(Y group),young exercise group(YE group),aging control group(A group)and aging exercise group(AE group),with 8 animals in each group.The experiment carried out exercise intervention in the way of running on the treadmill.All the exercise mice in each group received adaptive exercise with increasing load for one week,and then received formal aerobic exercise intervention for 12 weeks according to the protocol.HE,Mas-son and Sirius scarlet staining were used to observe the pathological morphology of liver tissue.The levels of Collagen Ⅰ and α-SMA in liver were observed by immunohistochemical staining.The mRNA expressions of miR-21,Collagen Ⅰ,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1)and SMAD7 in liver tissues were detected by q-PCR.Western Blot assay was used to detect the protein expressions of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TGF-β receptor Ⅱ(TβR-Ⅱ),Smad7 and P-Smad2/3 in liver tissues.Result:Compared with Y group,hepatocyte degeneration and fiber deposition were observed in group A.The mRNA and protein levels of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TβR-Ⅱ,P-SMAD2/3 and miR-21 in liver tissues were significantly increased(P<0.05),while the level of Smad7 was significantly decreased(P<0.05).After exercise intervention,liver tissue degeneration and fiber deposition were alleviated in the AE group,and the expressions of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TβR-Ⅱ,P-Smad2/3 and miR-21 in liver tissue were significantly decreased(P<0.05),the level of Smad7 was significantly increased(P<0.05).Conclusion:Aerobic exercise can effectively improve age-induced hepatic fibrosis.The underlying mechanism may be related to inhibiting the overexpression of TGF-β1,reducing the expression of TGF-β1/Smad signaling pathway related molecules,inhibiting miR-21,improving the activity of Smad7,and reducing the deposition of liver cell fibers.

Objective:To investigate the effect and underlaying mechanism of aerobic exercise on aging-induced hepatic fi-brosis.Method:Thirty-two SPF grade C57BL/6J male mice were used,including 16 mice aged 2 months(young group)and 16 mice aged 19 months(senescent group).Both the aging group and the young group underwent one week of acclimatization.The animals were randomly divided into four groups:young control group(Y group),young exercise group(YE group),aging control group(A group)and aging exercise group(AE group),with 8 animals in each group.The experiment carried out exercise intervention in the way of running on the treadmill.All the exercise mice in each group received adaptive exercise with increasing load for one week,and then received formal aerobic exercise intervention for 12 weeks according to the protocol.HE,Mas-son and Sirius scarlet staining were used to observe the pathological morphology of liver tissue.The levels of Collagen Ⅰ and α-SMA in liver were observed by immunohistochemical staining.The mRNA expressions of miR-21,Collagen Ⅰ,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1)and SMAD7 in liver tissues were detected by q-PCR.Western Blot assay was used to detect the protein expressions of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TGF-β receptor Ⅱ(TβR-Ⅱ),Smad7 and P-Smad2/3 in liver tissues.Result:Compared with Y group,hepatocyte degeneration and fiber deposition were observed in group A.The mRNA and protein levels of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TβR-Ⅱ,P-SMAD2/3 and miR-21 in liver tissues were significantly increased(P<0.05),while the level of Smad7 was significantly decreased(P<0.05).After exercise intervention,liver tissue degeneration and fiber deposition were alleviated in the AE group,and the expressions of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TβR-Ⅱ,P-Smad2/3 and miR-21 in liver tissue were significantly decreased(P<0.05),the level of Smad7 was significantly increased(P<0.05).Conclusion:Aerobic exercise can effectively improve age-induced hepatic fibrosis.The underlying mechanism may be related to inhibiting the overexpression of TGF-β1,reducing the expression of TGF-β1/Smad signaling pathway related molecules,inhibiting miR-21,improving the activity of Smad7,and reducing the deposition of liver cell fibers.

OBJECTIVE To study the toxicity of the extract from Mi ao medicine Wikstroemia indica to zebrafish . METHODS Zebrafish embryo model was used as the object ，after exposure to W. indica extract （10，20，40 μg/mL），the number of spontaneous twitching within 1 min，heart rate within 10 s，the occurrence of malformation and death were detected and recorded . Zebrafish was used as the object ，after exposure to W. indica extract（10-100 μg/mL）for 24，48 and 72 h，and the median lethal concentration（LC50）of W. indica extract to zebrafish at different time points were calculated . After exposure to low ，medium and high concentration （27，37，51 μg/mL）of W. indica extract，the liver phenotype ，hepatocyte apoptosis and lipid deposition of zebrafish were observed ，and the activities of alanine aminotransferase （ALT），aspartate aminotransferase （AST）and lactate dehydrogenase（LDH）in liver tissue were detected . RESULTS Compared with blank group ，the number of spontaneous twitching ， malformation rate （except for 10 μg/mL group ）and mortality of embryos increased significantly in 10，20，40 μg/mL groups of W. indica extract，and the heart rate （except for 10，20 μg/mL group ）of embryos decreased significantly （P＜0.05）. LC50 of W. indica extract to zebrafish at 24，48 and 72 h were 39.850，28.300 and 21.490 μg/mL，respectively. After drug treatment ，the transparency of liver area of zebrafish in low ，medium and high concentration groups of W. indica extract reduced and their shape were enlarged；apoptosis and lipid deposition increased ；the activities of ALT ，AST and LDH in liver tissue were significantly increased （P＜0.05）. CONCLUSIONS Miao medicine W. indica extract had develop mental toxicity to zebrafish embryos and he patotoxicity to zebrafish .