| Background&objectives:Pulmonary arterial hypertension(PAH)is considered as a group of disease with complicated etiology and poor prognosis.Especially pulmonary arterial hypertension associated connective tissue diseases,lacked of early and sufficient diagnosis,make treatment difficult in the clinical diagnosis.Microcirculation dysfunction is the key link in the pathogenesis of systemic sclerosis(SSc),the correlation of them is more and more recognized.Due to the many limitations of clinical research,animal model provides a great help for exploration of disease pathogenesis and diagnostic methods.We use models of bleomycin(BLM)and monocrotaline(MC T)induced SSc-PAH in rabbit,to explore the relationship between bulbar conjunctiva microcirculation and PAH and early predictive value.At the same time,vascular endothelial growth factor(VEGF)always has been confirmed by many researches,and plays an important role in vascular remodeling.We try to discuss the correlations of PAH and bulbar conjunctiva microcirculation and VEGF level,and further explore the signification of bulbar conjunctiva microcirculation in SSc-PAH.Methods:1.Twenty-four male New Zealand rabbits in total were randomly divided into three groups(solvent control group,model group and glucocorticoid group),each group of eight.Model group received intraperitoneal injection of 1% MCT once and abdominal subcutaneous injection of BLM 100ul(1mg/ml)daily,and glucocorticoid group received intraperitoneal injection of methylprednisolone(MP,2.6mg/kg,1mg/ml)in addition of the above,after three weeks drug-free.Then,measure the mean pulmonary arterial hypertension(mPAP)by the right heart catheterization and compare solvent control group to judge whether we successfully built the PAH model or not.By measuring the right ventricular hypertrophy index(RVHI)and perfecting histopathologic diagnosis,we evaluated whether the model fitted the SSc-PAH’s pathology.2.We analyzed the bulbar conjunctiva microcirculation and detected the expression of VEGF in serum by using the method of enzyme-linked immunosorbent assay(ELISA).Analysis the correlations of PAH and bulbar conjunctiva microcirculation and VEGF level,and diagnosis the value of bulbar conjunctiva microcirculation to SSc-PAH by ROC curve.Results:1.Compared with the solvent control group and the glucocorticoid group,the level of mPAP and RVHI in model group increased,which was statistically significant(P<0.05).2.Histopathologic examination: the slides of the skin tissues in model group showed skin atrophy and hyperkeratosis in skin lesions,and a few of lymphocytes and plasma cells infiltration in dermis;the slides of the lung tissues in model group showed massive hemorrhage in the alveolar,irregular thickening of small artery with muscularization forming the cluster structure,infiltration with lymphocytes and plasma cel s.3.The analysis of the bulbar conjunctiva microcirculation showed that the total integration of model group was significantly different from the other two groups,which mainly manifested in vascular thickening,vascular distortion,reticular malformation,bleeding,and vascular to ne,above items positively related to the mPAP(P < 0.05).4.The ROC curve analysis with total integral of the bulbar conjunctiva microcirculation showed that the area under the curve is 0.852(P < 0.05).A score of 5.2 points was the largest point of correct diagnosis index,as the diagnosing cut-off point,which sensitivity was 88.9%,and specificity was 75.0%.5.The serum level of VEGF in model group compared with the other two groups had significant difference(P < 0.05),which positively related to the total integral of the bulbar conjunctiva microcirculation(P < 0.05).Conclusion:1.Male New Zealand rabbits Receiving BLM and MCT’s injection can successfully establish the SSc-PAH model.2.To SSc-PAH,the bulbar conjunctiva microcirculation exits dys functions,the severity of that positively correlated with mPAP,especially in vascular thickening,vascular distortion,bleeding,reticular malformation,and vascular tone.3.The bulbar conjunctiva microcirculation total score of 5.2 or higher can be used as a diagnosis cut-off point of PAH,which sensitivity was 88.9%,and specificity was 75.0%.4.The serum level of VEGF in SSc-PAH is increased,associated with the bulbar conjunctiva microcirculation total score and mPAP. |
