| Objective This study aims to evaluate the therapeutic effect and dose effect of intraarticular injection of different doses of exosomes derived from Umbilical cord mesenchymal stem cells(MSC);The expression of ATF-3 and GAP-43 in DRG were detected,The repair of cartilage was detected by hematoxylin eosin(HE)staining,so as to explore how exosomes treatment relieves pain.Methods Ninety clean male SD rats were selected,and eighteen rats were selected by random number table method as the control group,and 50 ul normal saline was injected into the knee cavity of the left hind limb of the rats.The other rats were injected 4mg/50 ul MIA into the knee cavity of the left hind limb to establish an OA pain model.After the arthritis pain model was gradually stabilized for 2 weeks,the rats with successful modeling were randomly divided into MIA group,exosome group: low dose group(40ug / 100ul),medium dose group(100ug / 100ul)and high dose group(200ug / 100ul).Rats in the control group and MIA group were injected with 100 ul saline in the knee joint cavity of the left hind limb.The rats were injected with different concentrations of 100 ul exocrine body in the low,middle and high dose groups.Pain behavior was measured 1 day before modeling 7,14 days after MIA modeling,and 7,14,28 days after exosome administration in each group.Western blotting were used to detect the expression of ATF-3 and GAP-43 in DRG.HE were used to detect the cartiage repair on 1day before the modeling and 7,14 days after monoiodoacetate injection and 7,14,28 days after Exosome injection.Results1.Compared with the control group,mechanical and thermal pain thresholds in MIA group were significantly lower after modeling(P<0.001);after MIA application,ATF-3 and GAP-43 expression signifificantly increased on the 14 th day after MIA injection P<0,001),but on the 7th day after modeling,there was no significant difference between the expression levels of ATF-3 and GAP-43 and the control group(P>0.05)2.Compared with MIA group,the latency of the mechanical and thermal pain thresholds of rats in low,medium and high dose groups increased significantly 7 days after administration,and the difference was statistically significant until the 28 th day(P<0.05).And there was no significant difference between medium and high dose groups(P >0.05)3.Compared with MIA group,ATF-3 expression signifificantly decreased at medium、high dose groups(P<0.001)for at least 28 days,became signifificant within 7 days,and maintained a lower level 28 days;at low dose of group,became signifificant within 14 days,and maintained a lower level to 28 days(P<0.05);there was no difference in medium compared with the high groups(P>0.05).4.Compared with MIA group,GAP-43 expression signifificantly increased at medium、high dose groups(P<0.001)for at least 28 days,became signifificant within 7 days,and maintained a higher level 28 days;at low dose of group,GAP-43 expression began to increase on 28 days(P<0.05);there was no difference in medium compared with the high groups(P>0.05).5.After Exosome application,OARSI grade showed significant statistical difference on28 days compared the MIA group to the Exosome groups(P<0.05);there was no difference between exosome groups.There was no significant difference between MIA group and exosome group 7 ~ 14 days after intra-articular injection(P>0.05).Conclusions1.The analgesic effect of medium and high doses is better than that of low doses,but there is no dose-dependent relationship between medium and high doses and analgesic effect.Beyond a certain dose,the analgesic effect does not increase with the increase of dose.2.Exosome can alleviate the pain induced by monoiodoacetate adjuvant.The analgesic mechanism may be related to reduce nerve injury,promote nerve and cartilage repair,and the nerve repair occurs earlier than cartilage repair.It has important clinical value in the treatment of osteoarthritis dominated by neuropathic pain,which is ineffective to traditional drugs,and provides us with a new choice. |
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