| Objective:Type 2 diabetic models rats were prepared by feeding high-fat-high-glucose diet in combination with a low-dose streptozotocin (STZ),observed the characteristics of bone metabolism in type 2 diabetic rats, effects of GLP-1 a nalogues (Liraglutide) on the bone metabolism in type 2 diabetic rats were explor ed.Methods:90 normal SPF male rats were selected.20 of them were randomize d as normal group(NC group),Others were feeding high-fat-high-glucose diet in combination with a low-dose streptozotocin to prepare Type 2 diabetic rat mo del. Type 2 diabetic rats were randomly divided into three group:diabetic grou p (DM), low dose Liraglutide (400ug/kg) treatment group(LR-L), high dose Liragluti de (800ug/kg) treatment group(LR-H). liraglutide was injected subcutaneously e veryday; NC group and DM control group were injected with normal saline in same way. Body weight(BW) of the rats,fasting blood-glucose (FBG), diet con dition and mental state were recorded. Rats of four groups were killed at 4 w eeks after giving medicine, the bone density of rats was detected by dual-energ y X-ray diffraction. Blood and bone samples were collected for biochemical in dices measurement and were made as pathological specimens.Reslut:58 rats got T2DM, building rate:83%,① Body weight (BW) at the end of the experiment, NC group>DM group>LR-L、LR-H group. (P<0.05). ②Glucose metabolism indices:compared with NC group, Fasting plasma gluco se, Triacylglyceride, Total cholesterol、FIS、ISI and HOMA-IR in DM group、 LR-Lgroup and LR-H group were lower (P<0.05).compared with DM group, F PG、TG、Tc、HOMA-IR of LR-L group were lower, FPG、TCH. HOMA-IR of LR-H group were lower, the ISI of LR-L group and LR-H group were low er. (P<0.05), there was no significant difference between LR-L group and LR-H in these biochemical indices (P> 0.05).After 4-week treatment, LR-L group a nd LR-H group of ISI have a vary degrees improved and HOMA-IR have alle viated(P<0.05).③The rats of liver index of DM group>LR-L>LR-H group> NC group. (P<0.01).④Bone metabolism index:there was no significant differen ce in the four groups of serum P,Ca, CTX-1, BGP (P> 0.05).ALP of DM group was higher than NC group (P<0.01), ALP of LR-L group was Lower than that of NC group (P<0.01).⑤Differences of bone density:the bon e density of LR-L group、DM group and LR-H group were significantly lower than that of NC group(p<0.05),but no significant difference was found among DM group,LR-L group and LR-L group (P>0.05).⑥ompared with NC grou p, serum OPG、RANKL in DM group、LR-L group and LR-H group were h igher, serum level of sclerostin in DM group was higher.(P<0.05). OPG of L R-H group was higher compared with DM group (P<0.05),RANKL of LR-L group and LR-H group were lower compared with DM group (P<0.05).OPG/ RANKL of DM group were lower compared with NC group. OPG/RANKL of LR-L group and LR-H group were higher compared with DM group (P<0.0 5).⑦Observation of pathological section of bone tissue:Bone trabeculae was ri ch with wide width,continuous and adjacent bone trabecular spacing is smaller in NC group. Compared with NC group, Bone trabeculae became thinner,nu mber was reduced, bone trabeculae split was more obviously in DM group, ho wever, compared with DM group, bone trabeculae of LR-L group and LR-H gr oup were not obviously decreased, with regularly, continuous and intact arrange ment. There was no significant difference between LR-L group and LR-H so as to bone morphology.Conclusion:1)The T2DM rat model could be successfully induced by feeding high-fat-high-glucose diet, after 5 weeks, intraperitoneal injection of STZ 35 mg/kg, These r ats exhibited some characters in similar with human type 2 diabetes, such as h yperglycemia, dyslipidemia and insulin resistance, hyperinsulinemia. It may pro vide a successfully animal model of T2DM.2)Type 2 diabetic rats were set up by feeding high-fat-high-glucose diet in co mbination with a low-dose streptozotocin (STZ),these T2DM rats had diminish ed bone density, and pathological of bone tissue showed the bone resorption w as accelerated, but bone metabolic indices of serum BGP, CTX-1 has no ob vious change, and the serum of sclerostin and ALP was increased.3)Liraglutide reduced the FPG of type 2 diabetic rats, improved insulin resistan ce, increased insulin sensitivity, reduced TC, TG, RANKL level, increased the s erum of OPG, has obvious weight reduction.4) Pathological of diabetic rats bone tissue showed accelerated bone desorptio n. Liraglutide may inhibit bone reabsorption, but improved bone mineral densit y has not been obseverd. |
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