Study Of Correlation Between Idiopathic Pulmonary Fibrosis And Cylic Nucleotides

Objective To evaluate the relationship between idiopathic pulmonary fibrosis (IPF) patients and the level of cAMP and cGMP in the peripheral blood of IPF patients, and to find the functional status of glucocorticoid receptor of IPF patients, then to provide the experimental foundation of the application of cAMP for curing IPF.Methods 21 patients with IPF diagnosed by HRCT, lung biopsy pathology andpulmonary function test were selected and 10 HV (healthy volunteers) as controls. First,we obtain 2ml venous blood from each patient, which was dealed with EDTA disodiumanticoagulation, then extract serum with density gradient centrifugation method after icebath, then add 0.1ml serum into 2ml anhydrous alcohol, then centrifugate and put thesupernate into tube, after that centrifugate the leavings with 1 ml 75% alcohol, then putthe two supernate together and dissolve the leavings after stoved with acetic acid buffersolution, then take 0.10ml to get the measurements by radiation immunoassay, the kitcomes from isotope department of Chinese-medical collage of shang hai. Doing statisticaltreatment with t test and linear correlation analysis,the significant difference is p <0.05.Results 1.The cAMP in the blood plasma from patients with IPF is obviouslylower than that from HV, but the cGMP is obviously higher than that from HV, the ratioof cAMP/cGMP is lower than that from HV; 2. The level of cylic nucleotides in the bloodplasma from patients with IPF has linear correlation with lung function. 3; The cAMP inthe blood plasma from group of hormonal therapy effectively in patients with IPF ishigher than that from group of hormonal therapy validly, but the cGMP is on thecontrary.Discussion The research of modern medicine indicates that all phenomenon of lifein the organism depends on message transfer and regulations in or out of cell, and theprocess needs the messenger in or out of cell, the cAMP and the cGMP as the secondmessenger play important roles in regulating immunoreaction, cell proliferation anddifferentiation, keeping balance of relaxation and contraction of smooth muscle,homeostatic equilibrium of vessel, participating nervous activity, regulating geneticexpression, and so on. Recently, as the incidence rate increased, IPF has been one of hot spots in the researchof respiration. But the etiology of this disease is unknown, and the pathogenesy of thisdisease is unclear, and there is no specific treatment at present, the therapy at presentcould not improve the life quality and lengthen survival time in the patients with IPF.Glucocorticoid has been seen as a leading drug through international at present, but it'seffective only in 20% patients with IPF, and it is usually temporary response.Immunosuppression and cytotoxic drug not only have potentially severe side effect, butalso have basically negative attitude to the therapy of IPF. So finding the failure reason ofglucocorticoid therapy and the effective therapy is the most important task. Receptor theory believes: The biological effect of hormone is mediated by thehomologous receptor, glucocortcoid receptor is depended on the substrate of proteinkinase of cAMP, so, as the level of cAMP decreased, the combining ability ofglucocorticoid receptor decreased by the affection of phosphorylation of glucocortcoidreceptor, the function of receptor could revive as the level of cAMP in the cell; the cGMPcould inhibit phosphorylation of protein kinase of cAMP, so it could affect the functionof glucocortcoid receptor. This experimental result indicates: The cAMP in the blood plasma from patients with IPF is lower than that from HV, andthe cGMP is higher than that from HV, we could observe that the function ofglucocortcoid receptor in the patients with IPF is in a comparative low level, so thismaybe one of failure reasons with glucocorticoid therapy. According to the improvingextent to the lung function after glucocortcoid therapy, dividing the patients with IPF toeffective group and valid group, and finding the The cAMP in the blood plasma fromeffective group is higher than that from valid group, but the cGMP is on the contrary.This result indicates the level of cylic nucleotides in the cell has a close relationship withthe function of glucocortcoid receptor and therapeutic efficacy of glucocortcoid. The result of this experiment still finds cylic nucleotides have a close relationshipwith the variance of pathology and paysiology of IPF. Now it is clear that the cAMP inthe blood plasma could be seen as a good index of function of people's cholinergic nerve.Patients with IPF usually have hyoxemia, this could excite the peripheral chemoreceptor,excite vagus nerve, lead to deep and fast respiration. In addition, the pressureenhancement of pulmonary circulation will excite cardiopulmonary receptor in the atrium,ventricles and great vessels wall of pulmonary circulation, and the reflex effect is theincreas of the sympathetic tone and the decreas of the vagotony, so the vagus nervefunction of patients with IPF is in the place of excited status, so the level of cGMP is high.The acetylcholine (ACH) released by exciting vagus nerve affects M choline receptor,then the adenylcyclase is inhibited, and the ATP production decreases because of theoxygen deficiency, the two factors make the level of cAMP decreas; the increas ofpulmonary circulation pressure could excite the increas of ANF in the blood plasma, theANF could activate guanylate cyclase, so the production of the cGMP increases. Thebacterium or virus in the patients with IPF combining infection could affect the couple ofG protein and the adenylcyclase, finally the decreasing of information transfer make thedecreasing of cAMP density. Although the level of cylic nucleotides about the patientswith IPF yet be reported, this experimental result and the theory about cylic nucleotidesindicate: all kinds of factors affecting the cAMP production could not affect cGMP, allkinds of factors affecting the level of cGMP accompany with the converse developmentof cAMP. The breakthrough of one disease therapy always accompany with the clarity of thepathogenesy. Traditional theory believes that the impairment and fibrosis induced by theinflammation is the pathology feature of IPF, and believes that the inflammatory processplay a very important role. But the inflammatory reaction in the case of IPF with accuratediagnosis is not severe, and the anti-inflammatory therapy in the most patients does notget ideal effect. Researching results at present prefer the essence of IPF to be one ofabnormal reparation, so the anti-fibrosis drug of precluding the proliferation of lungfibroblast and over secreting collogen could interfere with the forming and growth in thetheory, and this could be hot spot of IPF therapy at present. Foreign researchers indicate that through the vitro cell experiment the cAMP possessesthe effect of anti-fibrosis and all the treatments which could improve the level of cAMPin the cell is beneficial to the therapy of IPF. Foreign research also indicates that all thefactors which could increase the level of cAMP in the cell could decrease the growingspeed of the cell and inhibit the proliferation of the cell; on the contrary, all the factorswhich could decrease the level of cAMP in the cell could increase the synthesis of DNAand the proliferation of the cell. So increasing the density of cAMP in the cell throughsupplying exogenous cAMP or other drugs may be a new idea of IPF therapy. Conclusion 1. The level of cAMP in patients with IPF is lower than HV, the level of cGMP inpatients with IPF is higher than HV.2. The expression of cylic nucleotides has associativity with pathology and physiology. 3. The expression of cylic nucleotides has relationship with impairing extent of lungfunction. 4. The level of cylic nucleotides has relationship with prognosis of glucocortcoid.