Effect of paclitaxel on mast cell-CCL2-macrophage axis in rats with pulmonary hypertension / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of paclitaxel on the mast cell-CCL2-macrophage axis in rats with pulmonary hypertension.Methods:Thirty SPF-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 180-220 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), pulmonary hypertension group (group PH), and paclitaxel group (group PTX). The model of pulmonary hypertension was established by subcutaneous injection of monocrotaline 60 mg/kg in rats.At 25 days after establishing the models, paclitaxel 2 mg/kg was injected via the tail vein once every four days, for 4 times in total in group PTX.The equal volume of normal saline was injected in the remaining 2 groups.The mean pulmonary artery pressure (mPAP) was performed at 40 days after establishing the model.The heart was removed and dried, the right ventricle (RV) and left ventricle plus ventricular septum (LV+ S) was weighed, and the Fulton index [RV/(LV+ S)] was calculated.The inferior lobe of left lung was taken, the ratio of media wall thickness of pulmonary vessels was calculated by HE staining, the number of Tryptase + , CD68 + , CD163 + , and Ki67 + cells was recorded by immunohistochemistry, the mean value was calculated, the percentage of Ki67-positive cells in blood vessels was recorded, and the proportion of muscularized blood vessels was calculated.The content of CCL2 was measured by enzyme-linked immunosorbent assay, and the expression of cleaved caspase-3 and Cyclin D1 was detected by Western blot. Results:Compared with group C, the mPAP, Fulton index, ratio of media wall thickness, proportion of muscularized blood vessels, the number of Tryptase + , CD68 + and CD163 + cells and percentage of Ki67 + cells were significantly increased, and the expression of cleaved caspase-3 was down-regulated in PH and PTX groups ( P<0.05), the expression of Cyclin D1 was significantly up-regulated in group PH ( P<0.05), and no significant change was found in group PTX ( P>0.05). Compared with group PH, the mPAP, Fulton index, ratio of media wall thickness, percentage of muscularized blood vessels, the number of Tryptase + , CD68 + and CD163 + cells and percentage of Ki67 + cells were significantly decreased, the expression of CCL2 and Cyclin D1 was down-regulated, and the expression of cleaved caspase-3 was up-regulated in group PTX ( P<0.05). Conclusion:The mechanism by which paclitaxel alleviates pulmonary hypertension is related to inhibiting the mast cell-CCL2-macrophage axis in rats.