ABSTRACT
OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.
ABSTRACT
Objective To establish a Hr mutant knockout mouse model to study the function of Hr gene.Methods Transcription activator-like effector nucleases ( TALENs) technique was used to disrupt the mouse Hr locus,creating heritable mutations that eliminate Hr function to explore the effects of Hr on hair development and provide a good model to study the function of Hr gene.The phenotype of Hr -/- mice was observed after birth and skin histology of the transgenic mice was studied by light microscopy.Results It was shown that a F0 mouse with the 2 -bp deletion in Hr gene ranging from 86 to 87 base pairs was obtained.The male mice with clear deletion of the Hr fragment and with obvious frame shifting were mated with wild-type female mice, and F1 mice were achieved.The heterozygous males mated with females to generate the F2 homozygous mice.The first hair coat of Hr-/- mice developed normally.Beginning from 14 days after birth, however, there was a rapid hair loss.The mices were completely hairless except for a few vibrissae at 30 days. Histologically, two characteristic structures appeared, the utriculus and dermal cyst.Conclusions The results suggest that Hr -/- mice are successfully created using TALENs, and Hr is important for regulating hair development, which could explain at least in part the hair loss and be applied to study the mechanism of hair growth and development disorder.