Objective: To investigate the effects of protein kinase C and breviscapine on the expression of pulmonary arterial collagen in chronic hypoxic rats.
Methods: Thirty-six rats were randomly divided into three groups: control group (A), hypoxic group(B),hypoxic + breviscapine(bre.)group (C). The ultrastructure of pulmonary arterioles was observed by electron microscope; the PKC activities of lung tissues were measured by radioactivity; the expression of PKC and collagen I and III in arterioles was observed by immunohistochemistry; the expression of procollagen I and III mRNA in arterioles was observed by in situ hybridization. The averages of integral light density( A )of PKC, collagen I and III and procollagen I and III mRNA in pulmonary arterioles were detected by image analysor and their relative contents were calculated.
Results: (1) The mean pulmonary arterial pressure (mPAP) and the weight ratio of RV to LV + S in group B were higher than those in group A(P < 0.01); the mPAP and the weight ratio of RV to LV + S in group C were lower than those in group B (P < 0.01). (2)Electron microscopy showed breviscapine could inhibit the deposition of collagenous fibers in pulmonary arterioles induced by hypoxia.(3) The total,cytosolic and particulate fractions of PKC activity and the ratio of particulate fraction to total PKC activity in group B were higher than those in group A(P < 0.01); the total,cytosolic and particulate fractions of PKC activity and the ratio of particulate fraction to total PKC activity in group C were lower than those in group B (P < 0.05). (4) The A values of PKC, collagen I and procollagen I mRNA in pulmonary arterioles were higher in group B than in group A(P < 0.01),and the A values of PKC, collagen I and procollagen I mRNA in pulmonary arterioles were lower in group C than in group B(P < 0.01); the differences in the A values of collagen III and procollagen III mRNA in pulmonary arterioles were not significant among the three groups (P > 0.05).(5)There were good correlations between the PKC activity of the lung tissues and the A values of collagen I and procollagen I mRNA in pulmonary arterioles(P < 0.05),and between the A values of PKC in pulmonary arterioles and those of collagen I and procollagen I mRNA in pulmonary arterioles(P < 0.01).
Conclusions: The PKC signal pathway regulates the expression of pulmonary arterial collagen in chronic hypoxic rats which may play an important role in the pathogenesis of pulmonary hypertension and structural remodeling of pulmonary arterials breviscapine can lower hypoxic pulmonary hypertension by inhibiting the effect of PKC and decreasing the expression of pulmonary arterial collagen.