Objective To observe the effects of Renshen Yimai Prescription on oxidative stress and vascular aging in ApoE-/-mice;To explore its mechanism of intervention in vascular aging.Methods Forty ApoE-/-mice were divided into model group,Western medicine group(rosuvastatin,2.6 mg/kg),TCM low-and high-dosage group(Renshen Yimai Prescription,4.29,8.58 g/kg),with 10 mice in each group.Another 10 C57BL/6J mice were set as normal group.A vascular aging model was established by ApoE-/-mice fed with a Western diet.Each medication group was given corresponding drugs by gavage for 12 consecutive weeks,the normal group and model group were given equivalent volume of pure water.HE staining and Masson staining were used to observe the morphological changes of aortic tissue,and ox-LDL content in serum was detected by ELISA,the contents of ROS,GSH,GPX and NAD+in serum were detected by colorimetric method,the expressions of SIRT1,p53,p21 and NOX4 protein in aortic tissue were detected by Western blot.Results Compared with the normal group,the model group mice showed significant fat deposition in the aorta,thickening of the intima and media,a significant decrease in elastic fibers,and an increase in collagen fibers;the serum contents of ox-LDL and ROS significantly increased(P<0.01),while the contents of GSH,GPX and NAD+significantly decreased(P<0.01);the expression of SIRT1 protein in the aortic tissue significantly decreased(P<0.05),the expressions of p21 and p53 protein significantly increased(P<0.01,P<0.05).Compared with the model group,a small amount of lipid deposition was observed in the intima of aorta in each medication group,with clearer membrane structures in each layer and reduced collagen fiber;the serum contents of ox-LDL and ROS in each medication group were significantly decreased(P<0.01),while the GSH content significantly increased(P<0.05,P<0.01),the NAD+content in TCM low-dosage group significantly increased(P<0.05);the expressions of p21 and NOX4 protein in aortic tissue of the TCM high-dosage group significantly increased(P<0.05,P<0.01).Compared with the Western medicine group,the TCM high-dosage group showed a significant decrease in ROS content(P<0.01)and a significant decrease in p53 protein expression(P<0.05).Compared with the TCM low-dosage group,the TCM high-dosage group showed a significant decrease in p21 protein expression(P<0.01)and a significant increase in NOX4 protein expression(P<0.01).Conclusion Renshen Yimai Prescription may reduce vascular endothelial damage by regulating oxidative stress levels and related protein expression,thereby playing a role in improving vascular aging.

OBJECTIVE To evaluate the effects of psoraleae crude polysaccharide(PPS) on metabolism and toxicity/efficacy relationship of coumarin components of Psoraleae Fructus(CCPF) by zebrafish integrated evaluation. METHODS Zebrafish(1-6 days post fertilization, dpf) was used to evaluate the safety of CCPF, PPS and their combination; the morphologies of zebrafish organs was observed and the number of deaths was recorded and the half death concentration of zebrafish(LC50) was calculated. Zebrafish(1-6 dpf) were exposed to CCPF and its combination with PPS; the dynamic changes of psoralenoside and isopsoralenoside and their metabolites psoralen and isopsoralen were analyzed. The zebrafish osteoporosis model was induced with 25 μmol·L-1 prednisolone; microscopic observation and digital imaging of zebrafish larvae of each treatment group cultured to 8 dpf were performed using alizarin red, and the bone staining area was quantitatively analyzed by image software to evaluate the anti-osteoporosis activity of above samples. RESULTS Evaluation of the safety of CCPF, PPS and their combination by interaction with zebrafish juveniles. The toxicity of the combination of CCPF and PPS to zebrafish was greater than that of CCPF or PPS alone, and the toxicity increased with the increase of the proportion of PPS: PPS reduced the poisoning concentration of zebrafish, causing serious morphological distortion of zebrafish organs, shortening the death time of zebrafish and increasing the death rate of zebrafish. PPS obviously accelerated the deglycosylation of psoralenoside and isopsoralenoside in CCPF into psoralen and isopsoralen, which were potential metabolites of liver injury. CCPF and its combination with PPS increased the mineralized area and cumulative optical density of zebrafish skull and the combination had a certain synergistic effect, which suggested that PPS increased the anti-osteoporosis activity of CCPF to some extent. CONCLUSION Based on the integrated evaluation of zebrafish, the effects of PPS on the metabolism and toxicity/efficacy relationship of CCPF are revealed, which provides an efficient method and idea for revealing the toxicity/efficacy relationship action of PPS on other structural components.