The Expressions Of PI3K, Akt1, Akt2, NF-κB In Bone Of Type2Diabetic Osteoporosis Rats

Objective:With the aging of the population process accelerating andthe incidence of type2diabetes increases gradually, the incidence of type2diabetes combined with osteoporosis is more and more high, and it affectspeople's quality of life severely. To investigate the expression changes ofintra-cellular correlation factor which participate in bone formation and boneresorption of type2diabetes combined with osteoporosis contributes to furtherclarify the effect on the development of this disease. PI3K/Akt signalingpathway is primary insulin signal transduction pathway, which is correlatedwith glycometabolism. In recent years, studies have found that cytokine PI3K,Akt1, Akt2, NF-κB can regulate bone metabolism because they are correlatedwith the proliferation and differentiation and so on of osteoblasts andosteoclasts.Currently the study about the expression of PI3K, Akt1, Akt2,NF-κB in bone of type2diabetes combined with osteoporosis is very few. Inthis study, we established type2diabetes combined with osteoporosis ratmodel, and at molecular level observed dynamicly the expression of PI3K,Akt1, Akt2, NF-κB in bone in order to investigate its possible effect on thedevelopment of this disease.Methods:100Wistar female rats, only2.5to3months, were randomlydivided into four groups after1week feeding: normal control group(shamgroup, NS, N=24), ovariectomy group(NOVX, N=26), type2diabetes controlgroup(sham group, DS, N=24), type2diabetic rats under ovariectomy group(DOVX, N=26). The weight of rats in the four groups had no significantdifference.The T2DM rats model was made by feeding them withhigh-sugar-fat feedstuff and injected small doses of STZ, and ovariectomied tomake the osteoporosis rats model. At4weeks,8weeks,12weeks afterovariectomy, five rats from every group were randomly selected and were executed after anesthesia, the femur and humerus of which were separated andused to extract RNA. The expression of PI3K, Akt1, Akt2, NF-κB at mRNAlevel in bone of every group was detected by RT-PCR. The experimental datawas presented as mean±standard deviation. Variance Analysis was used tocheck differences between groups by SPSS13.0, P<0.05was consideredstatistically significant.Results：1The expression of PI3K mRNA: At4weeks after ovariectomy, theexpression of PI3K in NOVX group is much higher than that in NSgroup(P<0.05), in DOVX group is much lower than that in DS group(P<0.05),in DS group is much higher than that in NS group(P<0.05), in DOVX group ismuch higher than that in NOVX group(P<0.05). At8weeks after ovariectomy,the expression of PI3K is no significant differences between NOVX and NSgroup(P>0.05), in DOVX group is much higher than that in DS group(P<0.05),there is no significant differences between DS and NS group(P>0.05). theexpression of PI3K in DOVX group is much higher than that in NOVXgroup(P<0.05). At12weeks after ovariectomy, the expression of PI3K inNOVX group is much higher than that in NS group(P<0.05), in DOVX groupis much higher than that in DS group(P<0.05),in DS group is much lower thanthat in NS group(P<0.05), in DOVX group is much lower than that in NOVXgroup(P<0.05).2The expression of Akt1mRNA: At4weeks after ovariectomy, theexpression of Akt1in NOVX group is much lower than that in NSgroup(P<0.05), in DOVX group is much lower than that in DS group(P<0.05),there is no significant differences between DS and NS group(P>0.05). theexpression of Akt1in DOVX group is much lower than that in NOVXgroup(P<0.05). At8weeks after ovariectomy, the expression of Akt1inNOVX group is much higher than that in NS group(P<0.05), there is nosignificant differences between DOVX and DS group (P>0.05). the expressionof Akt1in DS group is much lower than that in NS group(P<0.05),in DOVXgroup is much lower than that in NOVX group(P<0.05).At12weeks after ovariectomy, the expression of Akt1in NOVX group is much higher than thatin NS group(P<0.05), in DOVX group is much lower than that in DSgroup(P<0.05),in DS group is much lower than that in NS group(P<0.05), inDOVX group is much lower than that in NOVX group(P<0.05).3The expression of Akt2mRNA: At4weeks after ovariectomy, theexpression of Akt2in NOVX group is much higher than that in NSgroup(P<0.05), in DOVX group is much lower than that in DSgroup(P<0.05), there is no significant differences between DS and NSgroup(P>0.05). The expression of Akt2in DOVX group is much lower thanthat in NOVX group(P<0.05). At8weeks after ovariectomy, NOVX group ismuch higher than that in NS group(P<0.05),there is no significant differencesamong DOVX and DS group, DS and NS group, DOVX and NOVXgroup(P>0.05). At12weeks after ovariectomy, the expression of Akt2inNOVX group is much higher than that in NS group(P<0.05), in DOVX groupis much lower than that in DS group(P<0.05), in DS group is much lower thanthat in NS group(P<0.05), in DOVX group is much lower than that in NOVXgroup(P<0.05).4The expression of NF-κB mRNA: At4weeks after ovariectomy, theexpression of NF-κB is no significant differences between NOVX and NSgroup(P>0.05), in DOVX group is much lower than that in DS group(P<0.05),in DS group is much higher than that in NS group(P<0.05), there is nosignificant differences between DOVX and NOVX group(P>0.05).At8weeksafter ovariectomy, the expression of NF-κB in NOVX group is much higherthan that in NS group(P<0.05), in DOVX group is much lower than that in DSgroup(P<0.05), there is no significant differences between DS and NSgroup(P>0.05).The expression of NF-κB in DOVX group is lower than that inNOVX group(P<0.05).At12weeks after ovariectomy, the expression ofNF-κB in NOVX group is much higher than that in NS group(P<0.05), inDOVX group is much higher than that in DS group(P<0.05), in DS group ismuch higher than that in NS group(P<0.05), in DOVX group is much higherthan that in NOVX group(P<0.05). Conclusion：1The expressions of PI3K, Akt1,Akt2in bone of NOVX group rats is higherthan that of NS group rats with time delay.2The expressions of PI3K, Akt1, Akt2in bone of DS group rats is lower thanthat of NS group rats with time delay.3The expressions of NF-κB in bone of NOVX and DS group rats is higherthan that of NS group rats with time delay.4The expressions of PI3K, Akt1, Akt2in bone of DOVX group rats with timedelay show downtrend than that of NS,NOVX and DS groups rats.5The expressions of NF-κB in bone of DOVX group rats with time delayshow uptrend than that of NS,NOVX and DS groups rats.6The inhibition of the expressions of PI3K, Akt1, Akt2and the increase of theexpressions of NF-κB in bone may be one of the reasons in the developmentof Type2diabetes with osteoporosis.