Effects Of Intra-Articular Hypertonic Glucose Injections In Rat Osteoarthritis Model

Objective:To investigate the effect of intra-articular hypertonic glucose injection on MIA-induced rat model of osteoarthritis(OA)and its mechanism.Methods:Forty healthy SD rats(male,weighing 200-220 g)were randomly divided into the normal group,negative control group,betamethasone group and hypertonic glucose group.The rats OA model were induced by injecting 50 ?l of 3 mg MIA-containing reagent into the left knee joint,and the normal group rats were injected with 50 ?l saline into the left knee joint.Since 15th day after modeling,the negative control group was injected with 50 ?l of normal saline,betamethasone group was injected with 50 ?l of betamethasone solution,hypertonic glucose group was injected with 50 ?1 of 12.5%hypertonic glucose,while the normal group was not intervened.Injection was performed once a week for four weeks.Weights were recorded before modeling and on 43rd day after modeling,and general conditions were observed.Pain-related behavior(Paw withdrawal threshold,PWT)tests were performed before modeling and on 14th,43rd days after modeling.Serum TNF-? and IL-1? levels were measured by ELISA on 43rd day after modeling,and gross observation and histopathological scoring were performed on the left femoral condyles.Results:(1)On 43th day after modeling,the rats in the negative control,betamethasone and hypertonic glucose groups all presented shaggy,withered and yellow hair.Yet the rats in the betamethasone and hypertonic glucose groups were more active than the negative control group,and their left knees moved more smoothly than the negative control group,but not as smoothly as the normal group.The body weight of rats in the normal group was significantly higher than those in the other three groups(P<0.05).Moreover,rats in the betamethasone and hypertonic glucose groups exhibited higher body weight than the negative control group(P<0.05),while no statistically significant difference was found in body weight between the betamethasone and hypertonic glucose groups(P>0.05).(2)On 14th day after modeling,50%PWT values of rats decreased significantly except for the normal group(P<0.05).On 43th day after modeling,50%PWT of rats in the negative control,betamethasone and hypertonic glucose groups remained lower than the normal group,yet the 50%PWT values of the betamethasone and hypertonic glucose groups were significantly higher than the negative control group(P<0.05).(3)Compared to the normal group,the serum levels of IL-1? and TNF-?increased significantly in the other three groups(P<0.05).Compared to the negative control group,the IL-1? and TNF-? levels in the betamethasone and hypertonic glucose groups both decreased(P<0.05),yet the hypertonic glucose group exhibited IL-1? and TNF-? levels significantly higher than the betamethasone group(P<0.05).(4)Negative control,betamethasone and hypertonic glucose groups exhibited the gross score of cartilage surface significantly higher than the normal group(P<0.05),but the score did not differ significantly between the three groups(P>0.05).(5)The structure of articular cartilage was clearly visible under light microscopy in the normal group.In the negative control group,normal cartilage cells almost disappeared,and fibrous cartilage was formed on the cartilage surface.Besides,severe cell proliferation was observed,as well as serious cell disarrangement and matrix staining disappeared.In the betamethasone and hypertonic glucose groups,thinning of cartilage layer,significantly reduced cells and small amounts of fibrous cartilage were observed under light microscopy.Mankin's score was significantly lower in the normal group than the other three groups(P<0.05).Negative control group exhibited Mankin's score significantly higher than the other three groups(P>0.05).No significant difference was found in Mankin's score between the betamethasone and hypertonic glucose groups(P>0.05).Conclusions:(1)Hypertonic glucose effectively relieves KOA-induced pain?reduces the IL-1? and TNF-? levels and inhibits the development of inflammation,and improves joint mobility?general condition;(2)Hypertonic glucose has a certain protective effect on articular cartilage,and it has high safety and small side effects;(3)The effects of hypertonic glucose on KOA in rats might be related to red-uce the level of inflammatory factors,meanwhile weaken the conduction of pain,provide energy and so on.