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Aim To investigate the effect of non-T cell binding peptide(FNS007)on collagen type Ⅱ-induced arthritis(CIA)in mice and the possible mechanisms.Methods The CIA model was induced by intradermal injection of bovine CⅡ+Freunds adjuvant.At the clinical onset of CIA,mice were randomly divided into 6 groups: blank control group(Control),model group,ORENCIA(abatacept)group,FNS007 low dose(1.2 mg·kg-1)group,FNS007 middle dose(2.4 mg·kg-1)group and FNS007 high dose(4.8 mg·kg-1)group.FNS007 was given by intravenous injection on the first day of arthritis and every other day until the study was terminated on d 28 after injection of the drug.The paw thickness and the ankle joint width were measured,and the arthritis scores were recorded.At termination,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and level of anti-CⅡ antibody in serum were examined by enzyme-linked immunosorbent assay(ELISA).Bone injury was analyzed by X-ray imaging,and HE staining was conducted to observe the histopathologic changes and pathological score of ankle tissues.Results CIA models were successfully induced.Compared with CIA group,FNS007 high dose significantly reduced the paw thickness and the ankle joint left-right diameter,lowered arthritis scores in CIA mice,reduced serum concentrations of IFN-γ,IL-6 and anti-CⅡ antibodies,and lowered the radiographic and histologic scores.Compared with CIA group,FNS007 middle dose group showed marked reduction in the arthritis scores,IL-6 content in serum,and inhibion in the radiographic and histologic scores.The arthritis scores,concentration of IFN-γ,the radiographic and histologic scores were significantly reduced in FNS007 low dose group compared with those in model group.Conclusion FNS007 can effectively inhibit the progression of CIA through inhibiting T-cell activation and reducing inflammatory cytokines,anti-CⅡ antibodies,and histoclasia and bone destruction.
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Objective:To observe the effects of FNS007 on collagen Ⅱ-induced arthritis(CIA) rat models and investigate the underlying mechanism.Methods: CIA model was induced by intradermal injection of Freunds adjuvant and bovine CⅡ.Rats were randomly divided into six groups:normal control group,model group,methotrexate group,high,middle and low doses of FNS007 groups,with 12 rats in each group.FNS007 was gived by intravenous injection,the normal control and model group were administrated with PBS.Observing the paw thickness,ankle joint width and the arthritis scores in the CIA rats during the experiment.On d 22 after injection of the drug, all rats were killed.Interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6 (IL-6) and level of anti-CⅡantibody in serum were examined by enzyme-linked immunosorbent assay (ELISA).The pathological score and radiography of ankle joint were evaluated.Results: Data revealed that FNS007 treated groups showed a significant reduction in paw thickness,ankle joint width and the arthritis scores compared to model group (P<0.05,P<0.01),especially FNS007 high dose goup.The levels of TNF-α,IFN-γ,IL-6 and anti-CⅡantibodies in serum in high dose goup were significantly lower than those of model group(P<0.05,P<0.01).X-ray examination showed that FNS007 could significantly alleviate the damage of joint and decrease the radiographic scores.Pathological examination exhibited that FNS007 could significantly reduce pathological scores,alleviate inflammatory cell infiltration and synovial hyperplasia,improve the histopathological changes.Conclusion: FNS007 has a treating effect on CIA rats,and the mechanisms may be through competitive inhibition of T cell,inhibiting inflammatory cytokines and anti-CⅡantibodies secretion,regulating the abnormal immune responses.
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Objective To evaluate the effect of aminoguanidine on cell apoptosis induced by acute myocardial ischemia in rats.Methods Thirty adult male Sprague-Dawley rats,weighing 250-290 g,were randomly divided into 3 groups (n =10 each):sham operation group (group S),myocardial ischemia group (group Ⅰ),and aminoguanidine group (group AG).The model of acute myocardial ischemia was established by ligating the left anterior descending branch of the coronary artery of rats anesthetized with chloral hydrate.Aminoguanidine 100 mg/kg was intraperitoneally administrated at 6 h of ischemia in AG group,while the equal volume of normal saline was given instead of aminoguanidine in group Ⅰ.The chest was opened at 3 h after aminoguanidine administration and hearts were quickly removed for detection of apoptosis in cardiomyocytes (by TUNEL) and expression of Bcl-2 and Bax in cardiomyocytes (by immuno-histochemistry),and for microscopic examination with light microscope.Apoptotic rate was calculated.Results Compared with group S,the apoptotic rate was significantly increased,the expression of Bax was up-regulated,and the expression of Bcl-2 was downregulated and the ratio of Bcl-2/Bax was decreased in group Ⅰ.Compared with group Ⅰ,the apoptotic rate was significantly decreased,the expression of Bax was down-regulated,and the expression of Bcl-2 was up-regulated,and the ratio of Bcl-2/Bax was increased in group AG.The pathological changes of myocardial cells were significantly attenuated in AG group as compared with group Ⅰ.Conclusion Amionguanidine can inhibit apoptosis in cardiomyocytes and is helpful in mitigating injury induced by acute myocardial ischemia in rats.
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ObjectiveTo evaluate the effect of aminooxyacetic acid on focal cerebral ischemia injury in rats.MethodsEighty healthy male SD rats aged 2.5 month weighing 250-280 g were randomly divided into five groups( n ＝ 16 each):sham operation group(group S),cerebral ischemia group(group Ⅰ),aminooxoacetic acid low,medium and high dose groups(groups AL,AM and AH ).Focal cerebral ischemia was induced by occlusion of middle cerebral artery using a nylon thread with rounding tip which was inserted into right internal carotid artery in groups I,AL,AM and AH.Intraperitoneal amincoxoacetic acid 25,50 and 100 μmol/kg were administered at 3 h of ischemia in groups AL,AM and AH respectively,while equal volume of normal saline 1 ml/kg were injected in groups S and I.Neurological function was assessed and scored (0＝ no deficit,4＝ unable to move,unconscious) in 8 rats at 21 h after aminooxyacetic acid administration in each group.The animals were then sacrificed and the brains were removed for determination of the cystathionine beta-synthase (CBS) activities in cortex,hippocampus and striatum corpora.The other eight rats of each group were sacrificed at 21 h after amincoxoacetic acid administration for determination of the cerebral infarct volume.ResultsCompared with group S,the neurological deficit scores and the CBS activities in cortex and hippocampus were significantly increased,the infarct volumes were significantly enlarged in group Ⅰ ( P < 0.05).Compared with group Ⅰ,the neurological deficit scores and the CBS activities in cortex and hippocampus were significantly decreased,the cerebral infarct volumes were significantly reduced in groups AM and AH (P < 0.05).There was no significant difference in the above-mentioned variables between groups AL and Ⅰ.ConclusionAminooxoacetic acid can reduce focal cerebral ischemia injury by decreasing CBS activity and reducing H2 S production in rats.
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Objectiye To investigate the effect of L-arginine on pulmonary surfactant (PS) in the rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods Forty-eight adult male SD rats weighing 220-270 g were randomly divided into 4 groups:group Ⅰ control (group C);group Ⅱ LPS;group Ⅲ LPS 3 h + L-arginine(group L1);group Ⅳ LPS6 h + L-arginine(group L2). ALI was induced by intravenous (Ⅳ)LPS 5 mg/kg in LPS,L1 and L2 groups. L-arginine 500 mg/kg was given intraperitoneally at 3 or 6 h after LPS administration in group L1 or group L2. The animals were sacrificed at 3 h after L-arginine administration, eight animals were sacrificed at 6 h and 9 h after LPS in group C and group LPS. The lungs were immediately removed for determination of surfactant-protein (SP-A) mRNA expression and broncho-alveolar lavage fluid (BALF). The total phospholipid (TPL) and total protein (TP) concentrations in the BALF were measured. Results SP-A mRNA in the lung tissue and TPL concentration in BALF were significantly decreased while TP concentration in BALF was significantly increased in group LPS, as compared with control groups( P ＜ 0.01 ). L-arginine given at 3 h after LPS administration significantly attenuated the LPS-induced changes while L-arginine given at 6 h after LPS did not. Conclusion L-arginine can protect the lungs from LPS-induced injury by up-regulating PS-expression.
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Objective: To investigate the beneficial effect of NG-nitro-L-arginine(L-NA) on cerebral ischemic injury and the possible mechanism by evaluating the effect of nitric oxide synthase(NOS) inhibitor,L-NA,on the contents of aspartate,glutamate,glycine and?-aminobutyric acid(GABA),respectively,in striatum,hippocampus and cortex of rat brain following cerebral ischemia. Methods:The model of focal cerebral ischemia in rat was prepared.Rats were divided into sham-operated group,ischemic group and L-NA group.Each group was further divided into 3 subgroup(n=6 for each): the middle cerebral artery occlusion(MCAO) was maintained for 2,6 and 12h,respectively.L-NA(20 mg/kg,ip) was administrated after MCAO,two times a day,for 3 consecutive days.The changes of infarcted volume and the contents of amino acids were assayed. Results:The infarcted volume(IV%) was not significantly different among the ischemic groups with or without L-NA administrated 2 or 6 h after MCAO;and was markedly decreased in the ischemic group with L-NA administrated 12 h after MCAO(P
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AIM: To investigate the analgesic effect and possible mechanism of Fufang Xiaojingtong Capsule(Radix astragali;Radix paeoniae alba,Radix et Rhizoma ginseng,Radix rehmanniae praeparata;Rhizoma chuanxiong)(FFXJTC) on oxytocin-induced dysmenorrhea in rats. METHODS: Sixty rats were randomly divided into normal control group(control),dysmenorrhea model group(model),high dose(2.0 g/kg),middle dose(1.0 g/kg) and low dose(0.5 g/kg)groups of treatment by FFXJTC,and Tianqi Tongjing Capsule(TQTJC) group(2.0 g/kg).Diethylstilbestrol was continuously subcutaneous injection for 10 d once a day in rats of all groups except rats of control group.FFXJTC was administrated ig for 7 d in rats of all groups except for model group given distillated water.After administration of oxytocin(0.2U) in every rat,the frequency of stretching writhing was recorded within 30 min.The blood was drawn 1 h after administration of oxytocin.The contents of nitric oxide(NO)and malondiadehyde(MDA) and activities of SOD and GSH-PX were respectively determined in serum. The contents of 6-Keto PGF_(1?) and TXB_2 were respectively determined in plasma.Uterus was dissected and homogenated for endothelin(ET-1) measurement. RESULTS: Compared with that of model group,frequency of stretching writhing decreased significantly,the activities of SOD and GSH-PX were markedly enhanced,NO content increased and MDA content decreased in serum,and 6-Keto PGF_(1?) content increased and TXB_2 content decreased in plasma in FFXJTC group. CONCLUSION: FFXJTC has an analgesic effect on dysmenorrhea induced by oxytocin in rats,its mechanism may be related to anti-oxidization,decreasing the contents of TXA_2 and ET-1,increasing the contents of NO and PGI_2.
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AIM: The quality standard for Compound Xiaojingtong Capsule(Radix Astragali, Radix Ginseng, Radix Angelicae Sinensis, Rhizoma Chuanxiong, etc.) were studied. METHODS: The TLC method for identification of Radix Ginseng, Radix Angelicae Sinensis, Rhizoma Chuanxiong in these capsules were established. Astragaloside Ⅳ was determined by single wavelength TLC-scanning(? s=530nm). RESULTS: Radix Angelicae Sinensis, Rhizoma Chuanxiong and Radix Ginseng could be detected. Astragaloside Ⅳ showed a linear relationship at the concentration range of 1.1～5.5?g (r=0.9983). The average recovery was 100.1% and RSD was 1.59% (n=6). CONCLUSION: This method is suitable for the quality control of Compound Xiaojingtong Capsule.
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AIM: To observe the changes of endogenous hydrogen sulfide/cystathionine-?-lyase(H2S/CSE) system while acute lung injury induced by LPS in rats.METHODS: Eighty rats were randomly divided into six groups(n=8): Ⅰ,control group;Ⅱ,LPS 1 h group;Ⅲ,LPS 3 h group;Ⅳ,LPS 6 h group;Ⅴ,LPS 9 h group;Ⅵ,LPS 12 h group.The ALI model of rats was prepared with LPS.The rats were respectively killed at 1,3,6,9 or 12 h after administration of LPS.The morphological changes of lung tissues were observed by light and electron microscope.The lung coefficient and the wet-to-dry weight ratio were measured.The contents of IL-1? and IL-10 in serum,the H2S level in plasma and the CSE activity in lung tissue were respectively detected.RESULTS: ⑴ In LPS 1 h group,the morphology,the lung coefficient,the wet-to-dry weight ratio,the H2S level and the CSE activity showed no changes compared with the control group.The contents of IL-1? and IL-10 were increased compared with the control group(IL-1?,P