TRPV4 channel mediates the increase of pulmonary microvascular endothelial permeability in rats with chronic hypoxic pulmonary hypertension / 生理学报

The purpose of the present study was to investigate the effect of transient receptor potential vanilloid 4 (TRPV4) channel on the permeability of pulmonary microvascular endothelial cells (PMVECs) in rats with chronic hypoxia-induced pulmonary hypertension (CHPH), so as to clarify the mechanism of vascular endothelial dysfunction during the occurrence of pulmonary hypertension (PH). CHPH rat model was established by exposure to chronic hypoxia (CH) for 21 days. Primary PMVECs were cultured by adherent tissue blocks at the edge of the lung. The permeability coefficient of primary cultured PMVECs was detected by fluorescein isothiocyanate (FITC)-dextran. The structure of tight junction (TJ) was observed by transmission electron microscope. The expression of TRPV4 and TJ-related proteins, such as, Occludin, Claudin-5, ZO-1 were examined by real-time fluorescence quantitative PCR and Western blotting. The intracellular calcium concentration ([Ca

The protective effect of cyclosporine A on daunorubicin injured H9c2 cardiomyoblasts / 中国药理学通报

Aim To study the protective effect of cyclosporine A (CsA) on daunorubicin (DNR) injured H9c2 cardiomyoblasts. Methods H9c2 cells were pre-treated with CsA for 2 hours, then co-cultured with 1 μmol · L

Decreased amplitude of Ca²⁺i elevation induced by menthol in pulmonary arterial smooth muscle cells of pulmonary hypertensive rats / 生理学报

The study was designed to explore the alteration of intracellular calcium concentration ([Ca²⁺]i), induced by transient receptor potential melastatin 8 (TRPM8) channel-specific agonist menthol, in pulmonary arterial smooth muscle cells (PASMCs) between control and pulmonary hypertensive (PH) rats. PH rat models were established by means of chronic hypoxia (CH) and monocrotaline (MCT) injection, respectively. PASMCs from control and PH rats were cultured. The change of [Ca²⁺]i in PASMCs induced by menthol, and the effect of TRPM8 channel-specific antagonist BCTC on the change of [Ca²⁺]i, were observed. Cellular localization of TRPM8 was examined by using immunohistochemistry. Results showed that menthol increased [Ca²⁺]i in the control PASMCs both in Ca²⁺ -normal and Ca²⁺ - free Tyrode's solutions, and at the same time BCTC could inhibit these two kinds of elevations. Compared with the control group, elevations of [Ca²⁺]i were decreased notably in CH- and MCT-pretreated PASMCs superfused with 2 mmol/L Ca²⁺ - or 0 Ca²⁺ -Tyrode's solutions. Immunohistochemical localization experiments showed that the whole PASMCs were dyed brown except for the nucleus. This study verified that TRPM8 exists both in membrane and sarcoplasmic reticulum of PASMCs. In addition, CH- and MCT-pretreatment could independently down-regulate the Ca²⁺ influx and Ca²⁺ release mediated by TRPM8 channel.

Changes of MMP-2, MMP-9 contents in cerebral tissues and cerebral edema in cerebral ischemia-reperfusion rats / 第二军医大学学报

Objective To investigate the expression and activation of MMP-2, MMP-9 in cerebral tissues of cerebral ischemia-reperfusion rats and the effects of doxycycline on the cerebral edema. Methods Cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion (MCAO). The rats were randomly divided into a sham-operated and 6 reperfusion groups according to different reperfusion periods (3 h, 6 h, 12 h, 24 h, 72 h, and 120 h groups). Dry weight method was used to evaluate hemispheric water content of the ischemic side after treatment with doxycycline. Western blotting analysis and Gelatin zymography were used to determine the expression and activity of MMP-2 and MMP-9 in the ischemic cerebral tissues. Results The protein expression and activity of MMP-2 were significantly increased in the ischemia tissue at 3 h and 120 h after reperfusion(P0.05). The hemispheric water content of the ischemic side gradually increased with reperfusion periods compared with the sham-operated group. Dexycycline significantly reduced the hemispheric water contents compared with the normal saline at the same time points(P<0.05 or P<0.01). Conclusion MMP-2, MMP-9 can induce vasogenic brain edema by degrading basal membrane of capillary vessel. The alteration of MMP-2, MMP-9 expression and activities are likely associated with brain edema during cerebral ischemia-reperfusion.