| ObjectsWith high prevalence, osteoarthritis is becoming one of the most important public health prombles in the world,and there is no fundamental measure to cure it.Hyaluronicacid ,as a aheteropolysaccharide ,plays an important role in supporting and protecting articular cartilage in the joint. On the end of the latest international research, in this paper we studied the effects of oral hyaluronic acid in the prevention and treatment of OA in the following three aspects:(1) Build a cold stress-induced osteoarthritis model in mice(2) Observe the effects of oral HA on OA mouse from the perspective of prevetion.(3) Observe the effects of oral HA on experimental OA mouse from the perspective of treatment.(4) Study the pharmacokinetics of HA in OA mice.MethodsBased on the three aspects above of research,the experimental methods are as follows:(1) 20 male BALB/C mouse were randomly divided into control group and model group with ten animals in each group.The right knees of model group mice were stimulated with 6℃~ 8℃water continuously for 30 days, 1.5h/d ,with weight changes observed. Then the articular swelling degrees of right knees were measured by vernier caliper. The levels of TNF-а, rheumatoid factor(IgM) and HA in mice serum were detected by ELISA. The pathological slices of right knee joints were producted by HE dye.(2) 50 male BALB/C mice were randomly divided into five groups,including control, model and three intervention groups,with eight animals in each group. Control group were treated with NS,while Intervention groups were reveived cold water simulation-induce like that in model group, at the same time ,they were orally treated with different doses of HA respectively continuously for 30 days .Then joint.rticular swelling degree of right knees, serum TNF-а, HA; IgM and pathological section of right articulation of knee were carried to observe the effect of oral hyluronic acid.To evaluate the effects of orally administered macromolecular hyaluronic acid on the progression of articular cartilage degeneration in a mice model of osteoarthritis.(3)48 male BALB/C mice were randomly divided into six groups,including control, model, three intervention groups and positive control group,with eight animals in each group. OA mice model ,prepared as above methods,were intervened by oral HA, continuously for 7 days.Then joint articular swelling degree of right knees, serum TNF-а,HA,T-SOD,MDA, and pathological section of right articulation of knee were carried to observe the effect of orally administered hyaluronic acid.(4)The BALB/C mice were randomly divided into NS control group and HA administration group after weighing. The mice were given cold stimulation every day for 30 days to build the experimental mice OA model. The OA mice were treated with the oral administration with 0.9%NS and HA in the next day of the stimulation-ending date. Every 5 mice were randomly put to death to measure the serm HA levels at the time 0,0.5,1,1.5,2,4,8,12 and 24h,respectively. Then the pharmacokinetics was discussed.Results(1) Significant increases of articular swelling degree ,serum TNF-аand HA levels were observed in the mice model group compared with the blank group(P<0.01),while the level of IgM showed no significant difference(P>0.05). A series of pathological changes appeared in model group, including disordered articular cartilage cells, karyolysis or disappearing nucleus,obviously proliferation, calcification, adhesions of cartilage or synovial cells , and so on.(2) There was significant increase in the level of Serum TNF-аand serum HA in model group compared to the control group(P<0.05),while the level of IgM had no significant change(P>0.05),and the pathological section showed characteristics of osteoarthritis.The serological indicators and pathological sections of intervention group, middle dose group and high dose group especially, showed lesser extent of changes than those in model group.(3) After treatment,the articular swelling degree of the interventions groups were all lessened ,compared with model group(P<0.01). There is significant decrease in the level of Serum TNF-а, HA, T-SOD and MDA(P<0.05),especially in middle and high dose groups. The pathological section of intervention groups also showed characteristics of osteoarthritis.But Pathological changes is not less obvious compared with model group. (4) The serum HA levels in HA group appeared an absorption peak at 1.5 h and a synthetic peak of HA at 8h after an oral administration of HA.The AUC at 24h was 1027. 1027μg?h/L There were no changes in the NS control group and beared no absorption peak.Conclusions(1) The cold stress can induce the osteoarthritis in mice. The murine model of osteoarthritis is builded successfully preliminarily.(2) Oral HA on OA can effectively relieve symptoms and pathological processes of osteoarthritis in mice from the perspective of prevention.(3) Oral hylauronic acid which can improve some serum markers ,is effective on OA mice. But no obvious change was observed in pathology.(4) The blood concentration curve appeared double peaks and the AUC (0-24h) was 1027μg·h/L after oral treated with HA.
|
PDF Full Text Request