假蒟对去卵巢糖尿病骨质疏松大鼠血糖、骨代谢、氧化应激的影响

Therapeutic effect of Piper sarmentosum extract in ovariectomized rats with type 2 diabetes mellitus and osteoporosis

目的观察假蒟对去卵巢糖尿病骨质疏松大鼠血糖、骨代谢指标、氧化应激指标、骨小梁的影响,探讨其对去卵巢糖尿病骨质疏松大鼠的治疗作用及其机制。方法采用随机数字表法将大鼠分为模型组、格列本脲组、雌二醇(E_2)组、假蒟组和假手术组5组,每组10只。假手术组只切除双侧卵巢周围少许脂肪组织,其余4组切除双侧卵巢后予链脲佐菌素(STZ)诱导制备去卵巢糖尿病骨质疏松模型。格列本脲组采用格列本脲5mg/(kg·d)灌胃,E_2组采用E_2100μg/(kg·d)灌胃,假蒟组采用假蒟125mg/(kg·d)灌胃,模型组和假手术组采用0.9%氯化钠溶液8ml/(kg·d)灌胃。药物干预4周后,检测空腹血糖(FBG)、TC、TG、血钙(Ca)、血磷(P)、E_2、空腹胰岛素(FINS)、糖化血清蛋白(GSP)、骨钙素(OC)、碱性磷酸酶(AKP)、超氧化物歧化酶(SOD)、丙二醛(MDA)、晚期糖基化终末产物(AGEs)水平。HE染色观察骨组织病理形态学改变。结果干预后,假蒟组血清FBG、TC、TG、AKP、MDA、AGES水平均低于模型组,血清SOD活性高于模型组,差异均有统计学意义(均P<0.05)。假蒟组与格列本脲组血清FBG水平比较差异无统计学意义(P>0.05)。骨组织病理形态学观察:与假手术组比较,假蒟组骨小梁数量减少不明显,排列较规则,连续性、完整性较好。结论假蒟降糖效果非劣效于格列本脲,其可能通过改善高血糖状态、抗氧化应激,从而抑制去卵巢糖尿病骨质疏松模型大鼠骨代谢紊乱。

Objective To investigate the therapeutic effect of Piper sarmentosum （PS） extract in ovariectomized rats with osteoporosis and type 2 diabetes mellitus （T2DM） and to explore its mechanism. Methods Fifty SD female rats were randomly divided into 5 groups： sham operation group, model group, PS-treated group, glibenclamide （GLI）-treated group, and E2-treated group, 10 rats in each group. The ovariectomy was performed to induce osteoporosis in rats of last 4 groups and in sham operation group the ovaries were isolated but not resected. One week after operation, intraperitoneal injection of streptozotocin （STZ） 35mg/kg was given to induce diabetes in all 4 groups with ovariectomy. The rats in PS-treated group, GLI-treated group and E2-treated group were given with Piper sarmentosum extract[125mg/（kg·d）] , GLI [5mg/（kg·d）] or E2 [100μg/（kg·d）] by gavage for 4 weeks, respectively, while the rats in sham group and model group were given with equal volume of normal saline [8ml/（kg·d）]. After 4 weeks of treatment, the levels of fasting blood glucose （FBG）, total cholesterol （TC）, triglyceride （TG）, serum calcium （Ca）, serum phosphorus （P）, E2, fasting insulin （FINS）, glycated serum protein （GSP）, osteocalcin（OC）, serum alkaline phosphatase （AKP）, superoxide dismutase （SOD）, malondialdehyde （MDA）, and advanced glycosylation end products （AGEs） were measured. The histopathological examination with HE staining was performed on femoral bone tissue. Results Compared with the model group , the levels of serum FBG, TC, TG, AKP, MDA, AGES were significantly decreased, and the SOD activity was increased in the PS-treated group （all P〈0.05）. There was no significant difference in FBG level after treatment between GLC-treated group and PS-treated group （P 〉0.05）. The HE staining showed that the trabeculae displayed good continuity and integrity in the PS-treated group and the reduction of trabeculae was not obvious compared with the sham operation group. Conclusion The Piper sarmentosum extract can lower the plasma glucose level and alleviate the bone metabolism disorder in the ovariectomized rats with osteoporosis and T2DM.