摘要:ObjectiveTo investigate the oxidative stress state in migraine rats under fatigue state and the regulation effect of Naoan Dropping Pill on Nrf2/ARE signaling pathway of oxidative stress.MethodsProphylactic drug intervention was given to rats for 7 days.On the 6th day of administration,the fatigue state was simulated by intraperitoneal injection of polyI:C,and nitroglycerin was injected subcutaneously into the neck on the 7th day to create migraine model.Mechanical pain threshold,thermal pain threshold and grasping force were tested before and after modeling.After successful molding,the contents of MDA,GSH and SOD related indicators of oxidative stress in serum,and the expression of migraine efficacy related proteins CGRP,c⁃Fos and oxidative stress mechanism-related proteins Nrf2 and HO⁃1 in the trigeminal spinal tract nucleus were detected.ResultsMechanical pain threshold and thermal pain threshold in NTG model group and F⁃NTG model group were significantly lowered than those in blank group (P<0.01),and after the intervention of Naoan Dropping Pill,the mechanical pain threshold and thermal pain threshold in the intervention group were significantly increased than those in the model group(P<0.05).The serum MDA level of NTG model group and F⁃NTG model group was increased than that of blank group(P<0.01),SOD and GSH levels were increased than those in blank group(P < 0.01).After the intervention of Naoan Dropping Pill,the serum MDA level in the intervention group was lowered than that in the model group(P<0.01).The levels of SOD and GSH further increased(P<0.05).The expression levels of CGRP and c⁃Fos protein in the trigeminal spinal nucleus of rats in NTG model group and F⁃NTG model group were increased than those in blank group(P<0.05).Compared with the model group,the expression levels of CGRP and c⁃Fos protein in the trigeminal spinal nucleus of the intervention group were decreased to various degrees after the intervention of Naoan Dropping Pill(P<0.01).The expression of Nrf2 and HO⁃1 protein in the trigeminal spinal nucleus of rats in NTG model group and F⁃NTG model group was increased than that in blank group(P<0.05).Compared with the model group,the expression levels of Nrf2 and HO⁃1 protein in the trigeminal spinal nucleus of the intervention group were significantly increased after the intervention of Naoan Dropping Pill(P<0.01).ConclusionThere was oxidative stress response in NTG-induced migraine model rats,and the antioxidant defense pathway NRF2/ARE was activated.Fatigue state can aggravate oxidative stress in migraine rats.Naoan Dropping Pill has a certain therapeutic effect on migraine in rats under fatigue state,and can improve the oxidative stress state in migraine rats.
摘要:ObjectiveTo study the mechanism of action of Jinteng Qingbi Granules in the treatment of rheumatoid arthritis in model rats.Methods10 rats were randomly selected as the blank control group(A),and another 60 rats were used to establish RA model by collagen-induced arthritis.Fourteen days after modeling,the model rats with arthritis index(AI)score≥4 were randomly divided into model control group(B),low(C),middle(D)and high dose(E)groups of Jinteng Qingbi Granules,methotrexate group(F)and tripterygium wilfordii polyglycoside group(G),with 6 rats in each group.Group C,D and E were respectively given 1.05,2.1 and 4.2 g/kg Jinteng Qingbi Granules by intragastric administration,three times a day.Group F was given methotrexate 0.8 mg/kg by gavage every 4 days; group g was given 2.625 mg/kg tripterygium wilfordii polyglycoside by gavage three times a day.Group A and group B were given equal volume of 0.9% sodium chloride injection.All groups were given intragastric administration for 4 weeks.The joint index (AI) scores of each group were compared. The anti-inflammatory factor interleukin (IL)⁃10, transforming growth factor β1(TGF⁃β1),IL⁃1β,tumor necrosis factor⁃α(TNF⁃α)and IL⁃17 in peripheral blood were detected by ELISA.Immunohistochemistry was used to detect the expression of osteoprotegerin(OPG)/nuclear factor κB receptor activator ligand(RANKL)and CD34,and Microvessel density(MVD)count.ResultsCompared with group A,the levels of IL⁃10 and TGF⁃β1 in peripheral blood of rats in group B were decreased,but the levels of IL⁃1β, TNF⁃α and IL⁃17 increased(P<0.05).The expressions of OPG,RANKL and MVD in synovium of knee joint were increased(P<0.05).The joint swelling in group C,D,E,F and G was lighter than that in group B(P<0.05).In group C,D,E,F and G,the levels of IL⁃10,TGF⁃β1 and TNF⁃α in peripheral blood were increased,while the levels of IL⁃1β and IL⁃17 decreased(P<0.05).The expressions of RANKL and MVD in synovium of knee joint of rats in groups D,E,F and G were decreased(P<0.05),while the expression of OPG in synovium of knee joint of rats in groups C,D,E,F and G increased(P<0.05).ConclusionJinteng Qingbi Granules can affect the development of RA by inhibiting inflammatory response, angiogenesis, and OPG/RANKL expression ratio.
摘要:ObjectiveTo study the effects of Tangluoning on IRE1α-CHOP signaling pathway in rat dorsal root neurons(DRGn)under high glucose environment.MethodsSixty clean grade male SD rats were randomly divided into Tangluoning group(25 rats)and normal group(35 rats),and the crude drug of Tangluoning was given in the Tangluoning group with 2.5 g/(kg•d)and the same amount of distilled water was administered by gavage for the preparation of comparative serum.The dorsal root ganglion(DRG)used to prepare cell suspension was obtained from SD fetal rats.DRGn cells were inoculated into 6-well plate and randomly divided into 7 groups:normal group(group A cultured with blank serum),model group(group B cultured with 75 mmol/L glucose and blank serum),Tangluoning group(group C cultured with 75 mmol/L glucose+Tangluoning medicated serum),miR⁃211 inhibitor group(group D cultured 75 mmol/L glucose+blank serum culture+miR⁃211 inhibitor negative),miR⁃211 inhibitor control group(group d cultured with 75 mmol/L glucose+Tangluoning medicated serum culture+miR⁃211 inhibitor negative control),agonist traditional Chinese medicine group(group E cultured with 75 mmol/L glucose+Tangluoning medicated serum culture+miR⁃211 agonist)and agonist traditional Chinese medicine control group(group e cultured with 75 mmol/L glucose+Tangluoning medicated serum culture+miR⁃211 agonist negative control).After 24 hours of culture,q⁃PCR was used to detect the gene expression levels of miR⁃211,IRE1α,p⁃IRE1α,XBP1 and CHOP in DRGn cells;Fluorescence probe method was used to detect ROS expression in DRGn cells,xanthine oxidase technique was used to detect SOD activity in DRGn cells,and thiobarbital method was used to detect MDA level.ResultsCompared the levels of ROS,SOD,MDA,miR⁃211 mrna,IRE1α,XBP1 and CHOP in each group,the differences were statistically significant(P<0.01).Compared with group A,the levels of ROS,MDA as well as miR⁃211,IRE1α,XBP1,CHOP mRNA in group B were obviously heightened and SOD reduced obviously(P<0.01).Compared with group B,the levels of ROS,MDA as well as miR⁃211,IRE1α,XBP1,CHOP mRNA in group C and D were obviously reduced and SOD level of group C was higher than that of group B.Compared the levels of ROS,MDA as well as miR⁃211,IRE1α,XBP1,CHOP mRNA in group d with B,the differences were not statistically significant(P>0.05);compared with group B,the levels of ROS,SOD,MDA,miR⁃211,IRE1α,XBP1,CHOP mRNA in group E were obviously heightened,SOD reduced(P<0.01);compared the levels of ROS,SOD,MDA,miR⁃211,IRE1α,XBP1,CHOP mRNA in group e with group C,the differences were not statistically significant(P>0.05).ConclusionTangluoning could reduce the activity of IRE1α-CHOP pathway by down-regulating the expression of miR⁃211.
关键词:Tangluoning;diabetic peripheral neuropathy;dorsal root ganglion;inositol enzyme 1α⁃C/EBP homologous protein pathway;rats
摘要:ObjectiveTo evaluate the effect of emodin on ovarian function and sex hormone level in rats with polycystic ovary syndrome.MethodsTwenty-eight non-pregnant female Sprague Dawley rats with periodic regularity were randomly divided into four groups(7 rats/group),including control group,control+emodin group,polycystic ovary syndrome(PCOS)model group and model+emodin treatment group.PCOS model group and model+emodin group were injected with 4 mg estradiol valerate into the back muscle of rats to prepare PCOS model.After induction,rats in control+emodin group and model+emodin group were injected with emodin 25 mg/kg intraperitoneally.Rats in control group and PCOS model group were injected with the same amount of normal saline.All these groups were treated once a day for 14 days.The body weight of rats in each group was measured every week.After 14 days of treatment,peripheral blood was collected from tail vein of rats in each group,and serum was obtained by centrifugal separation for the related tests.After the rats in each group were killed by decapitation,samples of uterus and ovary tissues were collected,and the weights of ovaries and uterus were measured respectively.The sexual cycle of rats was measured,the ovarian mass/body mass and uterine mass/body mass were calculated,the histological changes of ovaries and uterus were observed by HE staining,and the levels of testosterone and anti Mullerian hormone(AMH)in plasma were measured.ResultsCompared with the blank control group,the estrus interval of the control+emodin group had no significant change(P>0.05).Compared with the blank control group,the proportion of estrus interval in PCOS model group was higher(P<0.05).Compared with PCOS model group,the proportion of estrus interval in model+emodin group was lower(P<0.05).Compared with the blank control group, the ovarian mass/body mass of rats in the control+emodin group had no significant change(P>0.05).Compared with the blank control group,the ovarian mass/body mass of PCOS model group was higher(P<0.05).Compared with PCOS model group,the ovarian mass/body mass of model+emodin group was lower(P<0.05).Compared with the blank control group,the uterine mass/body mass of rats in the control+emodin group had no significant change(P>0.05).Compared with the blank control group,the uterine mass/body mass of PCOS model group was lower(P<0.05).Compared with PCOS model group,the uterine mass/body mass of model+emodin group was higher(P<0.05).In PCOS group,a large fluid-filled cystic follicle appeared,its granular layer died off,and its membranous layer formed the inner wall of epithelial-like cell proliferation,and the cystic fluid contained macrophages.This phenomenon was not observed in the model+emodin group,and the tendency of follicle enlargement was not observed.Compared with the blank control group,the serum androgen level in PCOS model group was higher(P<0.05).Compared with PCOS model group,serum androgen level in model+emodin group was lower(P<0.05).Compared with the blank control group,the serum AMH level in PCOS model group was higher(P<0.05).Compared with PCOS model group,AMH level in model+emodin group was lower(P<0.05).ConclusionEmodin can improve the ovarian function of PCOS rats and keep the balance of the levels of various sex hormones.