Effect of Wenxin Prescription on G1/S Cell Cycle Transformation in Atherosclerosis Rats / 中国实验方剂学杂志

Objective:To observe the effects of Wenxin prescription on the key targets of gap 1/synthesis （G₁/S） cell cycle transformation in rats with atherosclerosis （AS）， and reveal the mechanism of Wenxin prescription in the treatment of AS. Method:Ninety SPF Wistar rats were randomly divided into a normal group （<italic>n</italic>=6） and a modeling group （<italic>n</italic>=84）. The rats in the modeling group were fed on a high-fat diet （4% cholesterol， 0.5% sodium cholate， 0.2% propyl thiouracil， 10% lard， 5% sugar， and 80.3% basal feed） for 60 days， and intraperitoneally injected with 400 000 U·kg^-1vitamin D₃， once a week for three weeks. The model rats were then randomly divided into a model group， high-dose （24 g·kg^-1）， medium-dose （12 g·kg^-1）， and low-dose （6 g·kg^-1） Wenxin prescription groups， and a rosuvastatin （1.8 mg·kg^-1） group. The groups with drug intervention were treated correspondingly by gavage for 30 days. The rats in the model group were administered with an equal volume of distilled water. The general condition of rats was observed after treatment. The levels of high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and total cholesterol （CHO） were detected by enzyme-linked immunosorbent assay （ELISA）， and the atherosclerosis index （AI） was calculated. The pathological morphology of the coronary artery and aorta was observed by hematoxylin-eosin （HE） staining. The protein and mRNA expression of E2F transcription factor 1 （E2F1）， phosphorylated retinoblastoma protein （p-Rb）， cell division cycle 25 （Cdc25）， CyclinE， and CyclinD₁ was detected by Western blot and real-time fluorescence-based quantitative polymerase chain reaction （Real-time-PCR）， respectively. Result:Compared with the normal group， the model group showed intima thickening， smooth muscle proliferation， and plaque formation in the coronary artery and aorta， decreased HDL-C （<italic>P</italic><0.01）， increased LDL-C， CHO， and AI （<italic>P</italic><0.01）， elevated protein and mRNA expression of E2F1， Cdc25， p-Rb， CyclinE and CyclinD₁ （<italic>P</italic><0.05）. Compared with the model group， the rosuvastatin group and the Wenxin prescription groups showed slight intimal hyperplasia and lumen narrowing of the coronary artery and aorta， decreased levels of LDL-C， CHO， and AI （<italic>P</italic><0.01）， and declining protein and mRNA expression of E2F1， Cdc25， p-Rb， CyclinE， and CyclinD₁ to varying degrees （<italic>P</italic><0.05）. Conclusion:Wenxin prescription can significantly inhibit the expression of key proteins and genes of the G₁/S cell cycle， regulate G₁/S cell cycle transformation， and reduce vascular smooth muscle and intimal hyperplasia in AS rats.