加味肾气丸联合髓芯减压术、人牙髓基质干细胞移植对兔早期激素性股骨头坏死的治疗作用研究

Therapeutic action of Jiawei Shenqi Pills combined with core decompression and human dental pulp stromal stem cells transplantation for early-stage steroid-induced avascular necrosis of femoral head in rabbits

目的观察加味肾气丸联合髓芯减压术、人牙髓基质干细胞(hDPSCs)移植对兔早期激素性股骨头坏死的治疗作用。方法将50只日本雄性大耳白兔随机分为正常组、模型组、髓芯减压组(以下简称髓减组)、髓芯减压+干细胞移植组(以下简称髓减干移组)、髓芯减压+干细胞移植+加味肾气丸组(以下简称髓减干移加味肾气丸组),每组10只。除正常组外其余各组均通过肌肉注射醋酸泼尼松龙注射液建立激素性股骨头坏死模型,正常组肌肉注射0.9%氯化钠注射液。正常组和模型组造模期间不予任何干预,髓减组于造模第4周给予髓芯减压术治疗,髓减干移组于造模第4周后予髓芯减压术+hDPSCs移植治疗,髓减干移加味肾气丸组在开始造模第1天即开始进行加味肾气丸灌胃治疗,每周2次,连续灌胃12周,于造模第4周后予髓芯减压术+hDPSCs移植治疗。比较各组造模第12周空骨陷窝率、血清血管内皮生长因子(VEGF)水平变化情况,并通过Micro CT检测计算各组造模第12周骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)、结构模型指数(SMI)、骨密度(BMD)变化情况。结果与正常组比较,模型组造模第12周空骨陷窝率升高(P<0.05);与模型组比较,髓减组、髓减干移组、髓减干移加味肾气丸组造模第12周空骨陷窝率均降低(P<0.05),且3个治疗组组间比较差异也均有统计学意义(P<0.05),髓减干移加味肾气丸组水平最低,其次是髓减干移组,最后是髓减组。与正常组比较,模型组造模第12周后血清VEGF水平降低(P<0.05);与模型组比较,髓减组、髓减干移组、髓减干移加味肾气丸组造模第12周血清VEGF水平均升高(P<0.05),且3个治疗组组间比较差异也均有统计学意义(P<0.05),髓减干移加味肾气丸组水平最高,其次是髓减干移组,最后是髓减组。与正常组比较,模型组造模第12周BV/TV、Tb.Th、Tb.N、BMD均降低(P<0.05),Tb.Sp、SMI均升高(P<0.05);与模型组比较,髓减组、髓减干移组、髓减干移加味肾气丸组造模第12周BV/TV、Tb.Th、Tb.N、BMD均升高(P<0.05),Tb.Sp、SMI均降低(P<0.05);3个治疗组组间比较,髓减干移组、髓减干移加味肾气丸组造模第12周BV/TV、Tb.Th、Tb.N、Tb.Sp、SMI改善均优于髓减组(P<0.05),髓减干移加味肾气丸组BV/TV、Tb.N、Tb.Sp、SMI改善均优于髓减干移组(P<0.05)。结论加味肾气丸联合髓芯减压术、hDPSCs移植治疗早期激素性股骨头坏死兔模型疗效确切,可有效促进坏死股骨头血管再生,改善局部血运,促进骨细胞增殖,促进骨组织修复,多种方案联合治疗具有明显优势。

Objective To observe the efficacy of Jiawei Shenqi Pills combined with core decompression(CD)and human dental pulp stromal stem cells(hDPSCs)transplantation for rabbits with early-stage steroid-induced avascular necrosis of femoral head(SANFH).Methods Fifty New Zealand white rabbits were randomly divided into Control group,Model group,CD group,Combination group 1(CD and hDPSCs transplantation),Combination group 2(Jiawei Shenqi Pills combined with CD and hDPSCs transplantation),with 10 cases in each.,the others groups were involved in modeling except for the blank group;the injection intervention of 0.9%sodium chloride in control group,in addition,the three treatments received prednisolone acetate injection to establish SANFH modle.In successful modeling,CD group and Combination group 1 recived intervention of CD or CD+hDPSCs transplantation on week 4,respectively;Combination group 2 recived gavage intervention of Jiawei Shenqi Pills on week 1(twice weekly[BIW]for 12 weeks),and received intervention of CD+hDPSCs transplantation on week 4.The changes of percentage of empty lacunae and serum vascular endothelial growth factor(VEGF)were compared on week 12 postoperative;as well as Micro Computed Tomography(CT)was used to detect and calculate bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular number(Tb.N),trabecular separation(Tb.Sp),structural model index(SMI),bone mineral density(BMD).Results On week 12 postoperative,the percentage of empty lacunae were increased in model group than that in control group(P<0.05);which in the three treatment groups were decreased in comparison with model group(P<0.05);there were statistically significant differences in the percentage of empty lacunae among the threes treatment group(P<0.05),the lowest level was common in Combination group 2,followed by Combination group 1 and CD group.On week 12 postoperative,serum VEGF was lower in model group than that in control group(P<0.05);which in the three treatment groups were increased in comparison with model group,(P<0.05);there were statistically significant differences in serum VEGF among the threes treatment group(P<0.05),the highest level was common in Combination group 2,followed by Combination group 1 and CD group.BV/TV,Tb.Th,Tb.N,BMD were decreased and Tb.Sp,SMI were increased in Model group in compared with those in control group(P<0.05),BV/TV,Tb.Th,Tb.N,BMD were increased and Tb.Sp and SMI were decreased in the three treatment groups than those in Model group(P<0.05).In comparison between groups,improvement of BV/TV,Tb.Th,Tb.N,Tb.Sp,SMI in Combination group 1,2 was better than that in CD group(P<0.05),improvement of BV/TV,Tb.N,Tb.Sp,SMI in Combination group 2 was better as comparison to Combination group 1(P<0.05).Conclusion For early-stage SANFH,Jiawei Shenqi Pills combined with CD and hDPSCs transplantation has a definite curative effect,which is capable of promoting SANFH angiogenesis,osteoblasts proliferation and bone repair,improving local blood supply.The combination of multiple treatments has obvious advantages.