当归腹痛宁滴丸体内调控原发性痛经相关通路的作用及其机制OA

Objective To explore the effect and mechanism of Danggui Futongning dropping pills(DNFD)in the treatment of primary dysmenorrhea.Methods ①Analgesic and anti-inflammatory experiments:60 Kunming mice were randomly divided into a model control group,DNFD low-,medium-,and high-dose groups,and an aspirin group,12 mice in each group.The analgesic and anti-inflammatory effects of DNFD were evaluated by intraperitoneal injection of 0.8%glacial acetic acid(0.01 mL·g-1),the hot plate method,and the ear swelling method.②Treatment of primary dysmenorrhea experiment:72 SD rats were randomly divided into a normal control group,a model control group,a low-dose,a medium-dose and a high-dose DNFD group and a Yimucao granules group.Except for the normal control group,the other groups were subcutaneously injected with estradiol valerate 2.0 mg·kg-1 on the 1st and 10th day,and estradiol valerate 1.0 mg·kg-1 on the 2nd to 9th days.The primary dysmenorrhea model was induced by the combined injection of estradiol valerate and oxytocin.From the 4th day of injection,the normal control group and the model control group were given an equal volume of 0.9%sodium chloride solution,and the other groups were given different doses of DNFD solution 2 mL for 7 consecutive days.To evaluate the effects of DNFD on writhing response,pathological changes of uterine tissue,contents of β-endorphin(β-EP),estradiol(E2),progesterone(PROG)and interleukin-6(IL-6)in serum,contents of prostaglandin E2(PGE2),cyclooxygenase-2(COX2),15-hydroxyprostaglandin dehydrogenase(PGDH)and cyclooxygenase-1(COX1)related to prostate metabolism,levels of oxidative stress superoxide dismutase(SOD)and malondialdehyde(MDA),and expressions of proteins related to Janus kinase(JAK)-nuclear factor kappa B signal transducer and activator of transcription signaling pathway/mitogen-activated protein kinase signaling pathway(NF-κB/STAT/MAPK)pathway in uterine tissue.Results ① Compared with the model control group,after administration of DNFD,the number of writhings in mice decreased,the degree of ear swelling decreased significantly(P<0.01),and the inhibition rate of ear swelling and pain threshold increased significantly(P<0.01).② Compared with the normal control group,the writhing times of rats in the model control group were significantly increased(P<0.01),the levels of E2,IL-6,tumor necrosis factor-α(TNF-α)and PGE2 in serum were significantly increased,the levels of PGDH,COX2 and COX1 mRNA were significantly increased(P<0.01),and the contents of β-EP and PROG were significantly decreased(P<0.01).The content of MDA increased,and the activity of SOD decreased significantly(P<0.01).The infiltration of inflammatory cells in uterine tissue was obvious;the expression of NF-κB,STAT3,JAK1,JAK2,N-terminal kinase(JNK),extracellular signal-regulated kinase(ERK),p38 mitogen-activated protein kinase(P38)and Bcl-2-associated X(BAX)protein in uterine tissue increased significantly,and the content of Bcl-2 decreased significantly.Compared with the model control group,after the administration of DNFD,the levels of E2,IL-6,TNF-α and PGE2 in serum decreased,the levels of PGDH,COX2,and COX1 mRNA decreased significantly(P<0.01),and the contents of β-EP and PROG increased significantly(P<0.01).The content of MDA decreased,and the activity of SOD increased significantly(P<0.01).And the histopathological improvement was obvious;the expression of NF-κB,STAT3,JAK1,JAK2,JNK,ERK,P38,and BAX protein in uterine tissue was significantly decreased,and the content of Bcl-2 was increased.Conclusion DNFD has analgesic and anti-inflammatory effects,and it exerts anti-dysmenorrhea effects by synergistically inhibiting NF-κB/STAT3/MAPK inflammatory signaling network and apoptosis.