| Objective: To evaluate the efficacy of Yao recipe Fuding Decoction in the treatment of experimental chronic non-bacterial prostatitis(CNP)and investigate the underlying mechanism by observing the effect of this recipe on the general condition,whole blood viscosity,wet prostate wei ght,histopathological changes,the levels of inflammatory cytokines TN F-?,IL-6 and IL-8,and the total expression level of proteins p38 MAP K,p-p38 MAPK and MMP-9 in CNP rats,for the purpose of providing experimental references for the clinical application of Yao recipe Fudin g Decoction in the treatment of CNP.Methods: Sixty adult male Sprague-Dawley rats were randomly and eve nly divided into 6 groups,i.e.the normal group,model group,positive group(tamsulosin hydrochloride sustained-release tablets),and high-,m eddle-,and low-dose Fuding Decoction groups.Except rats in the norm al group,all rats in other groups were used to establish experimental C NP rat models through subcutaneous injection of estradiol benzoate(0.25 mg/Kg·30d)into the neck and back one day after castration under st erile conditions following anesthetization by intraperitoneal injection of 10% chloral hydrate(0.3 ml/100g).After successful modeling was confi rmed,the above medicines were administered.The concentrations of Fu ding Decoction(as those of crude drugs)used in the high-,middle-,an d low-dose Fuding Decoction groups were 3.9667 g/ml,1.9833 g/ml,an d 0.9917 g/ml,respectively;the positive group was given a suspension of tamsulosin hydrochloride sustained-release tablets at a concentration o f 0.0023 mg/ml.All rats in these groups were intragastrically administer ed at a ratio of 1 ml/100 g bodyweight.The normal group and the mo del group were given normal saline of the same volume intragastrically once a day for 30 consecutive days.Observation indicators included:(1)Macroscopic conditions of each group of rats during the experiment,such as mental state,body weight changes,etc.;(2)Whole blood viscosit y in each group of rats;(3)Changes in prostate appearance and wet pro state weight in each group of rats;(4)Pathological changes of prostate ti ssue in each group of rats;(5)Levels of TNF-?,IL-6,and IL-8 in seru m of each group as detected using the Elisa method;(6)Total expressio n level of proteins p38 MAPK,p-p38 MAPK,and MMP-9 in prostate tis sues of each group as detected by Western blot.Results:(1)Rats in the normal group were in good condition,the diet was normal,and the hair was bright.For rats in other groups,dietary activities decreased after modeling started,the hair became rough,and t he body weight at the end of modeling was statistically different from that in the normal group(p < 0.05).After administration,the overall c ondition of rats in each medication group improved.By the end of the experiment,the body weight of each group was markedly higher than that of the model group(p < 0.05);there was no significant difference in body weight between the high-dose Fuding Decoction group and th e normal group(p ? 0.05);the body weight of the positive group and the middle-and low-dose Fuding Decoction groups was lower than tha t of the normal group and the high-dose Fuding Decoction group(p <0.05).(2)The prostates in the normal group were ruddy and soft,withou t adhesion to the surrounding tissues.The prostates in the model groupwere atrophic to different degrees,dark red or gray,and hard,adhered to the surrounding tissue fascia.As compared with the model group,t he positive group and all three Fuding Decoction groups had improved prostates,which became lightened or reddish,soft,and less adhesive to the surrounding tissues and atrophic.Relative to the normal group,the wet weight of prostates was significantly lower in the model group,th e positive group,the mid-and low-dose Fuding Decoction groups(p <0.05);no difference existed between the high-dose Fuding Decotion gr oup and the normal group(p ? 0.05);the wet weight of prostates in t he high-and middle-dose Fuding Decoction groups was higher than tha t in the model group(p < 0.05);the wet weight of prostates in the po sitive group and the low-dose Fuding Decoction group somewhat increa sed,but was not statistically different from that of the model group(p ? 0.05);the wet weight of prostates in the high-dose Fuding Decoction group was higher than that in the positive group and the low-dose Fu ding Decoction group(p < 0.05).As compared with the model group under the light microscope,the pathological changes of prostate tissue i n rats were improved,interstitial fibrosis and inflammatory cell infiltrati on reduced,the secretion in ductal lumen increased,and the repair of t he damaged prostate tissue cells was promoted in all Fuding Decoction groups to different degrees.In terms of prostate histopathological infla mmation scores,the model group,positive group,middle-and low-dose groups were different from the normal group and the high-dose group(p < 0.05),whereas no difference existed between the high-dose group and the normal group(p ? 0.05).Our data show that the high dose of Fuding Decoction had the best improving effect on prostate tissue lesi ons in CNP rats.(3)The viscosity of whole blood at various shear rates in the mod el group was significantly higher than that in the normal group(p<0.05);as compared with the model group,the whole blood viscosity at va rious rates in CNP rats in the middle-and high-dose Fuding Decoction groups decreased significantly(p < 0.05),the high-dose group having better effect;the whole blood viscosity at low shear rates in the high-d ose group was lower than that in the low-dose group and the positive group(p < 0.05).(4)As compared with the normal group,the levels of serous TNF-?,IL-6,and IL-8 in the model group,the low-and middle-dose groups were higher(p < 0.05);the positive group and the high-dose group h ad higher levels of TNF-? and IL-6(p < 0.05).Relative to the model group,the levels of TNF-?,IL-6,and IL-8 were lower in the positive group and the high-dose group(p < 0.05),the levels of TNF-? and IL-8 were lower in the middle-dose group(p < 0.05),and the levels of TNF-?,IL-6,and IL-8 in the low-dose group decreased but the differen ce was not statistically significant(p ? 0.05).Compared with the positi ve group,the level of TNF-? in the high-dose group was decreased(p < 0.05),and the level of TNF-? and IL-8 in the low-dose group was higher(p < 0.05).The levels of TNF-?,IL-6,and IL-8 were lower in the high-dose group than in the low-dose group(p < 0.05),the level o f TNF-? in the middle-dose group was lower than those in the low-dos e group(p < 0.05),and the level of TNF-? in the high-dose group wa s lower than that in the middle-dose group(p < 0.05).(5)As compared to the normal group,the total expression levels o f proteins p38 MAPK,p-p38 MAPK,and MMP-9 protein in the prostate tissue of the model group significantly increased(p < 0.05);the expres sion level of p-p38 MAPK decreased(p < 0.05)and that of MMP-9 increased(p < 0.05)in the positive group;the expression level of total p38 MAPK protein in the high-dose group was decreased(p < 0.05);the expression level of p-p38 MAPK protein in the middle-and high-dose groups was higher(p < 0.05);the expression level of total p38 MAPK and p-p38 MAPK proteins was higher in the low-dose group(p < 0.05).Compared with the model group,the expression levels of p38 MAPK,p-p38 MAPK,and MMP-9 decreased in the positive group and all Fudin g Decoction groups(p < 0.05).Compared with the positive group,the expression level of p-p38 MAPK was higher(p < 0.05)and that of M MP-9 decreased(p < 0.05)in all Fuding Decoction groups;the express ion level of total p38 MAPK protein in the high-dose group was decreas ed(p < 0.05).The expression level of total p38 MAPK protein in the high-dose group was lower than that in the low-dose group(p < 0.05).Conclusion:(1)Yao recipe Fuding Decoction can improve the overall c ondition of CNP rats,reduce the degree of pathological changes,restore wet prostate weight and secretion function to a certain extent,reduce i nflammatory cell infiltration of prostate tissue,and promote the repair o f damaged prostate tissue,indicating that this medicine has improving e ffect on CNP rats.(2)The mechanism underlying the therapeutic effects of Yao reci pe Fuding decoction on CNP may be:(1)improving the local microcircu lation disturbance in the prostate by reducing the viscosity of whole blo od to enhance the permeability of prostate tissue and increase the blood concentration;(2)reduceing the levels of inflammatory cytokines TNF-?,IL-6,and IL-8 by immunomodulation;(3)inhibiting the expression of p38 MAPK,p-p38 MAPK,and MMP-9 in the prostate tissue via the P38 MAPK signaling pathway to improve inflammation symptoms. |
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