促胰液素对去卵巢骨质疏松大鼠血清骨转换指标和骨密度的影响
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摘要
目的观察促胰液素(secretin,SCT)对去卵巢骨质疏松大鼠骨转换指标和骨密度的影响。方法采用双侧卵巢去除法制备绝经后骨质疏松大鼠模型,将60只SD大鼠随机分为假手术组、模型对照组、雌激素治疗组和促胰液素治疗组,每组各15只。干预3个月后,测定腰椎骨密度(bone mineral density,BMD),采取ELISA法测定血清I型胶原N前端肽(procollagen I N-Terminal propeptide,PINP)和I型胶原C末端肽(collagen type I C-terminal cross-linked telopeptide,CTX),另使用STRING10.0蛋白相互作用网络分析工具分析骨质疏松相关差异蛋白。结果与假手术组比较,模型对照组、雌激素治疗组、促胰液素治疗组的PINP含量升高(P<0.05),模型对照组的CTX含量升高(P<0.05),模型对照组的BMD下降(P<0.05),雌激素治疗组和促胰液素治疗组的CTX、BMD含量无显著差异(P>0.05);与模型对照组比较,雌激素治疗组、促胰液素治疗组PINP、CTX含量有所下降,而BMD含量升高(P<0.05);雌激素组与促胰液素组之间PINP、CTX、BMD含量无显著差异(P>0.05)。结论促胰液素能改善去卵巢骨质疏松大鼠的PINP和CTX含量,增加骨密度,抑制骨质丢失,具有较好的抗骨质疏松效果。
Objective To observe the effect of secretin(SCT) on bone turnover biomarker and bone mineral density(BMD) in ovariectomized rats with osteoporosis. Methods A rat model of postmenopausal osteoporosis was prepared by bilateral ovarian removal. Sixty SD rats were randomly divided into sham operation group, control group, estrogen treatment group, and SCT treatment group, with 15 rats in each group. After 3 months of treatment, BMD of the lumbar vertebrae was measured. Serum procollagen I N-Terminal propeptide(PINP) and collagen type I C-terminal cross-linked telopeptide(CTX) were determined with ELISA. In addition, osteoporosis-related proteins were analyzed using a protein interaction network analysis tool(STRING 10.0). Results Compared with the sham operation group, the PINP levels in the model control group, the estrogen treatment group, and the secretin treatment group increased(P<0.05), and the CTX levels in the control group increased(P<0.05). BMD in the control group decreased(P<0.05). There was no significant difference in the levels of CTX and BMD between the estrogen-treated group and the SCT treatment group(P>0.05). Compared with the control group, the levels of PINP and CTX in the estrogen-treated group and the secretin treatment group decreased, while BMD increased(P<0.05). There was no significant difference in the levels of PINP, CTX, and BMD between the estrogen group and the SCT treatment group(P>0.05). Conclusion SCT improves the levels of PINP and CTX, increases BMD, and inhibits bone loss in osteoporosis ovariectomized rats. It has better anti-osteoporosis effect.
Objective To observe the effect of secretin(SCT) on bone turnover biomarker and bone mineral density(BMD) in ovariectomized rats with osteoporosis. Methods A rat model of postmenopausal osteoporosis was prepared by bilateral ovarian removal. Sixty SD rats were randomly divided into sham operation group, control group, estrogen treatment group, and SCT treatment group, with 15 rats in each group. After 3 months of treatment, BMD of the lumbar vertebrae was measured. Serum procollagen I N-Terminal propeptide(PINP) and collagen type I C-terminal cross-linked telopeptide(CTX) were determined with ELISA. In addition, osteoporosis-related proteins were analyzed using a protein interaction network analysis tool(STRING 10.0). Results Compared with the sham operation group, the PINP levels in the model control group, the estrogen treatment group, and the secretin treatment group increased(P<0.05), and the CTX levels in the control group increased(P<0.05). BMD in the control group decreased(P<0.05). There was no significant difference in the levels of CTX and BMD between the estrogen-treated group and the SCT treatment group(P>0.05). Compared with the control group, the levels of PINP and CTX in the estrogen-treated group and the secretin treatment group decreased, while BMD increased(P<0.05). There was no significant difference in the levels of PINP, CTX, and BMD between the estrogen group and the SCT treatment group(P>0.05). Conclusion SCT improves the levels of PINP and CTX, increases BMD, and inhibits bone loss in osteoporosis ovariectomized rats. It has better anti-osteoporosis effect.
引文
[1] Paschalis EP,Gamsjaeger S,Hassler N,et al.Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality[J].Bone,2017,95:41-46.
[2] Kimura S,Saito M,Kida Y,et al.Effects of raloxifene and alendronate on non-enzymatic collagen cross-links and bone strength in ovariectomized rabbits in sequential treatments after daily human parathyroid hormone (1-34) administration[J].Osteoporos Int,2017,28(3):1-11.
[3] 中华医学会骨质疏松和骨矿盐疾病分会.原发性骨质疏松症诊疗指南(2017)[J].中华骨质疏松和骨矿盐疾病杂志,2017,20(5):413-443.
[4] 张玉卓,沈耿杨,张志达,等.激素联合去卵巢诱导大鼠股骨骨质疏松复合模型的建立[J].中国组织工程研究,2017,21(24):3858-3863.
[5] 黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9):1069-1072.
[6] 金华,刘志军,颜春鲁,等.贝那普利和氨氯地平对自发性高血压大鼠促胰液素、生长抑素表达的影响[J].中国应用生理学杂志,2018(2):154-158.
[7] 胡斌杰.益气活血方在消化性溃疡愈合过程中对胃肠激素影响的研究[D].南京:南京中医药大学,2016.
[8] 黄祝,戈一峰,靖俊,等.促胰液素对早期妊娠小鼠子宫内膜基质细胞cPLA_2和mPGEs-1表达的影响[J].生理学报,2016,68(6):725-732.
[9] 柳力公,周吕.油酸钠对大鼠肠粘膜促胰液素细胞的影响[J].基础医学与临床,1994,14(4):61-63.
[10] 肖小芹,舒圆月,邓桂明,等.乌药水提液对腹泻型肠易激综合征模型大鼠Ghrelin、MTL、SP、Sec水平的影响[J].湖南中医药大学学报,2017,37(5):477-480.
[11] 金华,刘志军,颜春鲁,等.镇肝熄风汤对自发性高血压大鼠促胰液素、生长抑素mRNA表达的影响[J].中国老年学杂志,2016,36(22):5493-5495.
[12] 白永愉,李强,金约朋,等.质子泵抑制剂对犬胰腺外分泌功能影响的研究[J].肝胆胰外科杂志,2016,28(1):55-58.
[13] Motojima Y,Kawasaki M,Matsuura T,et al.Effects of peripherally administered cholecystokinin-8 and secretin on feeding/drinking and oxytocin-mRFP1 fluorescence in transgenic rats[J].Neuro Res,2016,109:63-69.
[14] 张颖,杨永滨.促胰液素对小脑浦肯野细胞抑制性突触的调节[J].哈尔滨医科大学学报,2015,49(5):393-396.
[15] 冯正平,孟平.消化系统疾病与骨质疏松症的研究进展[J].中国骨质疏松杂志,2004,10(4):514-516.
[16] 吴倩倩.炎症性肠病患者的骨代谢和骨密度分析[D].上海:复旦大学,2014.
[17] 邵丽华,王强,张维,等.溃疡性结肠炎患者骨密度变化及其相关因素的研究[J].国际消化病杂志,2014,34(4):264-266.
[18] 宋敏,周灵通,刘小钰,等.消化系统疾病并发骨质疏松症与肠道菌群的关系探讨[J].中国骨质疏松杂志,2018,24(1):130-134.
[19] Duggan SN,O'Sullivan M,Hamilton S,et al.Patients with chronic pancreatitis are at increased risk for osteoporosis[J].Pancreas,2012,41(7):1119-1124.
[20] Vujasinovic M,Maisonneuve P,Hedstr?m A,et al.Deficiency of fat-soluble vitamins,minerals and trace elements in patients with chronic pancreatitis of different etiology[J].Pancreatology,2018,18(4):S106-S107.
[21] Lin SY,Hsu WH,Lin CC,et al.Effect of acute pancreatitis on the risk of developing osteoporosis:A nationwide cohort study[J].PloS One,2017,12(6):e0179358.
[22] 唐天悦,翟振亚,谭成全,等.半胱胺在猪营养上的研究进展[J].动物营养学报,2018,30 (5):1-8.
[23] He WT,Liang BC,Shi ZY,et al.Weak cation exchange magnetic beads coupled with matrix-assisted laser desorption ionization-time of flight-mass spectrometry in screening serum protein markers in osteopenia[J].Springerplus,2016,5(1):679.
[24] 沈耿杨,任辉,江晓兵,等.去卵巢大鼠不同时期骨量、骨转换指标、雌激素水平的变化规律及相关性[J].中国组织工程研究,2015,19(2):170-176.
[25] 孙振双,徐道明,朱媛媛,等.温肾固疏方调控去卵巢大鼠氧化应激及骨代谢指标的机制研究[J].中国骨质疏松杂志,2017,23(6):740-744.
[26] 史晓林,梁博程,姚建亮,等.基于TMT标记联合LC-ESI-MS/MS技术筛选绝经后骨质疏松症的血清分子标志物研究[J].中华骨科杂志,2015,35(10):1004-1010.
[2] Kimura S,Saito M,Kida Y,et al.Effects of raloxifene and alendronate on non-enzymatic collagen cross-links and bone strength in ovariectomized rabbits in sequential treatments after daily human parathyroid hormone (1-34) administration[J].Osteoporos Int,2017,28(3):1-11.
[3] 中华医学会骨质疏松和骨矿盐疾病分会.原发性骨质疏松症诊疗指南(2017)[J].中华骨质疏松和骨矿盐疾病杂志,2017,20(5):413-443.
[4] 张玉卓,沈耿杨,张志达,等.激素联合去卵巢诱导大鼠股骨骨质疏松复合模型的建立[J].中国组织工程研究,2017,21(24):3858-3863.
[5] 黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9):1069-1072.
[6] 金华,刘志军,颜春鲁,等.贝那普利和氨氯地平对自发性高血压大鼠促胰液素、生长抑素表达的影响[J].中国应用生理学杂志,2018(2):154-158.
[7] 胡斌杰.益气活血方在消化性溃疡愈合过程中对胃肠激素影响的研究[D].南京:南京中医药大学,2016.
[8] 黄祝,戈一峰,靖俊,等.促胰液素对早期妊娠小鼠子宫内膜基质细胞cPLA_2和mPGEs-1表达的影响[J].生理学报,2016,68(6):725-732.
[9] 柳力公,周吕.油酸钠对大鼠肠粘膜促胰液素细胞的影响[J].基础医学与临床,1994,14(4):61-63.
[10] 肖小芹,舒圆月,邓桂明,等.乌药水提液对腹泻型肠易激综合征模型大鼠Ghrelin、MTL、SP、Sec水平的影响[J].湖南中医药大学学报,2017,37(5):477-480.
[11] 金华,刘志军,颜春鲁,等.镇肝熄风汤对自发性高血压大鼠促胰液素、生长抑素mRNA表达的影响[J].中国老年学杂志,2016,36(22):5493-5495.
[12] 白永愉,李强,金约朋,等.质子泵抑制剂对犬胰腺外分泌功能影响的研究[J].肝胆胰外科杂志,2016,28(1):55-58.
[13] Motojima Y,Kawasaki M,Matsuura T,et al.Effects of peripherally administered cholecystokinin-8 and secretin on feeding/drinking and oxytocin-mRFP1 fluorescence in transgenic rats[J].Neuro Res,2016,109:63-69.
[14] 张颖,杨永滨.促胰液素对小脑浦肯野细胞抑制性突触的调节[J].哈尔滨医科大学学报,2015,49(5):393-396.
[15] 冯正平,孟平.消化系统疾病与骨质疏松症的研究进展[J].中国骨质疏松杂志,2004,10(4):514-516.
[16] 吴倩倩.炎症性肠病患者的骨代谢和骨密度分析[D].上海:复旦大学,2014.
[17] 邵丽华,王强,张维,等.溃疡性结肠炎患者骨密度变化及其相关因素的研究[J].国际消化病杂志,2014,34(4):264-266.
[18] 宋敏,周灵通,刘小钰,等.消化系统疾病并发骨质疏松症与肠道菌群的关系探讨[J].中国骨质疏松杂志,2018,24(1):130-134.
[19] Duggan SN,O'Sullivan M,Hamilton S,et al.Patients with chronic pancreatitis are at increased risk for osteoporosis[J].Pancreas,2012,41(7):1119-1124.
[20] Vujasinovic M,Maisonneuve P,Hedstr?m A,et al.Deficiency of fat-soluble vitamins,minerals and trace elements in patients with chronic pancreatitis of different etiology[J].Pancreatology,2018,18(4):S106-S107.
[21] Lin SY,Hsu WH,Lin CC,et al.Effect of acute pancreatitis on the risk of developing osteoporosis:A nationwide cohort study[J].PloS One,2017,12(6):e0179358.
[22] 唐天悦,翟振亚,谭成全,等.半胱胺在猪营养上的研究进展[J].动物营养学报,2018,30 (5):1-8.
[23] He WT,Liang BC,Shi ZY,et al.Weak cation exchange magnetic beads coupled with matrix-assisted laser desorption ionization-time of flight-mass spectrometry in screening serum protein markers in osteopenia[J].Springerplus,2016,5(1):679.
[24] 沈耿杨,任辉,江晓兵,等.去卵巢大鼠不同时期骨量、骨转换指标、雌激素水平的变化规律及相关性[J].中国组织工程研究,2015,19(2):170-176.
[25] 孙振双,徐道明,朱媛媛,等.温肾固疏方调控去卵巢大鼠氧化应激及骨代谢指标的机制研究[J].中国骨质疏松杂志,2017,23(6):740-744.
[26] 史晓林,梁博程,姚建亮,等.基于TMT标记联合LC-ESI-MS/MS技术筛选绝经后骨质疏松症的血清分子标志物研究[J].中华骨科杂志,2015,35(10):1004-1010.