不同数量的骨髓间充质干细胞移植对去卵巢大鼠骨质疏松的影响

Effects of transplantation with different amount of bone marrow mesenchymal stem cells on osteoporosis in ovariectomized rats

目的比较不同数量的骨髓间充质干细胞(BMSCs)移植对去卵巢大鼠骨质疏松的影响。方法将40只雌性Spraguedawley(SD)大鼠随机分为假手术组和去卵巢组,3个月后验证造模成功,再将去卵巢组大鼠随机分为单纯去卵巢组(OVX组)、雌激素治疗组(E2组)、低剂量BMSCs移植组(BMSCs2×10^6,LS组)、中剂量BMSCs移植组(BMSCs4×10^6,MS组)、高剂量BMSCs移植组(BMSCs6×10^6,HS组)。LS组、MS组、HS组分别经尾静脉移植对应剂量的BMSCs,E2组肌注雌二醇。在干预后的第8、12和16周时用双能X线骨密度仪测量全身骨密度,干预16周后取胫骨做苏木精-伊红染色法(HE染色)。结果OVX组的全身骨密度(BMD)和骨小梁占骨髓腔面积的比例均降低(P<0.05)。各BMSCs移植组的全身BMD及骨小梁占骨髓腔面积的比例均较OVX组高(P<0.05),且随着所移植干细胞数量的增加而增高,HS组的骨密度和骨小梁占骨髓腔面积比例为最佳。结论移植BMSCs可以明显改善去卵巢大鼠的骨质疏松,随着所移植BMSCs数量的增加可以获得更好和更长久的疗效。

Objective To investigate the effects of transplantation with different amount of bone marrow mesenchymal stem cells(BMSCs)on osteoporosis in ovariectomized rats. Methods The rat model of osteoporosis was prepared by ovariectom(OVX)and verified after 3 months.A total of 60 female Sprague-Dawley rats were randomly divided into 6 groups(n=10 each). The rats with shamed operation served as a sham-injured control group(sham control group). The 5 ovariectom(OVX)groups with osteoporosis were study groups as follows:(1)the negative therapy group(simple OVX group);(2)the positive therapy group(OVX+ estrogen, E2 group)by intramuscular injection;others were treated with transplantation of BMSCs by tail vein injection in low dose(LS group), middle dose(MS group)and high dose(HS group). At 8, 12 and 16 weeks after intervention, body mineral density(BMD)were detected by dual-energy x-ray absorptiometry scans.After 16 weeks of intervention, rat shinbone was obtained and stained by hematoxylin-eosin(HE)staining. Results Compared with the sham control group, simple OVX group showed a reduced total body BMD and the decreased proportion of trabecular bone to bone marrow cavity area(P<0.05). The total body BMD and the proportion of trabecular bone to bone marrow cavity area were higher in each BMSCs transplantation groups than in simple OVX group at 8, 12, 16 weeks after intervention(P<0.05), which showed a increased trend in the total body BMD and the proportion with the increased dose of transplantation BMSCs(P<0.05). Rats in the HS group had highest BMD and best proportion of trabecular bone to bone marrow cavity area among three doses of transplantation BMSCs. Conclusions BMSCs transplantation can significantly improve osteoporosis of ovariectomized rats with an increased total body BMD and higher proportion of trabecular bone to bone marrow cavity area, and better and longer outcomes can be achieved.