Fundamental Study On The Effect And Mechanism Of GP-prednisone On Experimental Idiopathic Pulmonary Fibrosis In Rats

Objective: To study the effect of Gypeno-sides (GP) on IdiopathicPulmonary Fibrosis (IPF). Idiopathic Pulmonary Fibrosis (IPF) is a progressive and usually fatallung disease charactered by fibroblast proliferation and extracellularmatrix remodeling, which result in irreversible distortion of the lung'sarchitecture. Because the pathogenetic mechanisms remain to be determined,and the clinically effective therapy is deficient, the prognosis of thisdiease is not better. According to the survey of epidemiology, the annualpercentage rate of this disease is about 0.7-1‰ whin people commonly agedbetween 50-70 years old, whose livability are less than 3 years. And itis also indicated that with the age developing, the incidence andmortality of this disease is increasing. Therefore, it is important tostudy the pathogenetic mechanisms and find the new way of therapy and thenew effective medicine. Gypeno-sides (GP) is a effective ingredient of Gynostemmapentaphyllum.As the literature shows, it has many pharmacological effects. Such asantioxidation, reducing the high cholesterin, eliminating the tumour andso on. In this thesis, aiming directly at pathologic status of thefundamental period in Idiopathic Pulmonary Fibrosis, we observed thecharacteristics of TCM syndromes at 7d, 14d, as well as observed the efectsof GP-prednisone on IPF rats model induced by bleomycin.Methods: the experimental research includes three parts as following:1. Experment study on the effect of GP-prednisone on IPF1.1 The effect of GP-prednisone on lung index in IPF rats 154 male SD rats, were divided into 7 groups(11 rats in each group)as sham-operation group, model control group, positive medicine groupⅠ, positive medicine groupⅡ, and high,moderate and low GP-prednisonegroups. The groups were operated in 7days,14days these two times. Forrats in the model control group, positive medicine groupⅠ, positivemedicine groupⅡ, and high,moderate and low GP-prednisone groups wereinjected with bleomycin A5 by trachea, for rats in sham-operation groupinjected with the same volume normal saline. From 24 min after modeling,GP-prednisone solution of different dosages(0.26g/kg,0.13g/kg,0.065g/kg)was given to rats in the high,moderate and low GP-prednisone group bygavage respectively, at the same time equal volume of normal saline wasgiven to those in the sham-model control group and model control group,and an equal volume of prednisone(20mg/kg,0.24g/kg) was given to thosein positive medicine groups. On the 7th day and the 14th day, taking 8 ratsfrom each group and weighing the lung, then assaying lung index.1.2 The effect of GP-prednisone on the content of HYP in IPF ratsThe content of disposal is the same as mentioned above. On the 7th day andthe 14th day, taking out the lung, collecting the blood of each group, thenadopted the method of literature to calculate the content of HYP in IPFrats.1.3 The effect of GP-prednisone on the content of HA in IPF ratsThe content of disposal is the same as mentioned above. On the 7th day andthe 14th day, collecting the blood of each group, then adopted the methodof ABC-ELISA to calculate the content of HA in IPF rats.2. The effect of GP-prednisone on the content of TNF-αin IPF ratsThe content of disposal is the same as mentioned above. On the 7th day andthe 14th day, collecting the blood of each group, then adopted the methodof ABC-ELISA to calculate the content of TNF-αin IPF rats.3. The effect of GP-prednisone on thymus in IPF ratsThe content of disposal is the same as mentioned above. On the 7th day andthe 14th day, taking out and weighing the thymus, then assaying the thymusindex, at the same time we observed the changes in pathomorphology(HEstaining).Results: the results showed as following1. The phenomena of lung index increasing in IPF rats manifested that theIPF rat model induced by bleomycin was successfully duplicated. Comparedwith model group, it revealed that in GP-prednisone treated rats: lungindex was dropped.2. Hyp content had not obvious difference on the 7th day, but on the 14th,Hyp content of m...