肾素-血管紧张素系统双轴对股骨头缺血性坏死的影响

Influence of renin angiotensin system biaxial on avascular necrosis of femoral head

目的探讨肾素-血管紧张素系统(RAS)双轴对非创伤性股骨头缺血性坏死(INFH)的影响。方法收集2015年10月—2017年6月于华中科技大学同济医学院附属协和医院及湖北省随州市中心医院骨科行股骨头置换术的90例患者,其中45例INFH患者作为INFH组,45例创伤性股骨颈骨折术后患者作为对照组。术前检测两组患者循环血中的血管紧张素转换酶(ACE)、血管紧张素Ⅱ(AngⅡ)、血管紧张素Ⅱ-1受体(AT1R)、ACE2、Ang(1-7)、Mas受体(Mas-R)的表达情况,术后检测股骨头局部骨组织中的ACE、AngⅡ、AT1R、ACE2、Mas-R、破骨细胞分化因子(RANKL)及骨保护素(OPG)mRNA的表达情况,并进行免疫组化分析。结果两组循环血中ACE、AngⅡ、AT1R、ACE2、Ang(1-7)及Mas-R表达情况比较,差异均无统计学意义(P>0.05)。INFH组股骨头局部骨组织ACE2、Mas-R、OPG mRNA表达水平均低于对照组(P<0.05),而ACE、AngⅡ、AT1R、RANKL mRNA表达水平及RANKL mRNA/OPG mRNA均高于对照组(P<0.05)。与对照组比较,INFH组骨组织HE染色显示组织内脂肪细胞增生,骨小梁变细,骨细胞核固缩、深染,骨陷窝空虚明显增多;INFH组骨组织Masson染色显示深蓝色变浅,较为杂乱,显示胶原结构减少、纤维结构明显增生。免疫组化结果提示INFH组骨组织中ACE及AT1R表达高于对照组,而ACE2及Mas-R表达低于对照组。两组ACE、AT1R、ACE2及Mas-R四组分阳性表达面积百分比比较,差异有统计学意义(P<0.05)。结论RAS双轴[ACE/AngⅡ/AT1R轴和ACE2/Ang(1-7)/MAS轴]在正常与INFH患者骨组织局部中表达差异,可能参与调节局部骨转换及骨坏死的进程,为后续研究及诊疗提供新的思路。

Objective To investigate the influence of renin angiotensin(RAS)biaxial on patients with ischemic necrosis of the femoral head(INFH).Methods From October 2015 to June 2017,90 patients underwent femoral head replacement in the Department of Orthopedics in Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology and Suizhou Central Hospital in Hubei Province were selected.Among them,45 patients with INFH were served as INFH group,and 45 patients with postoperative traumatic femoral neck fracture were served as control group.The expressions of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),angiotensinⅡ-1 receptor(AT1R),ACE2,Ang(1-7),Mas receptor(Mas-R)in the circulating blood of two groups were detected before operation,and the expressions of ACE,AngⅡ,AT1R,ACE2,Mas-R,receptor activator of NF-κB ligand(RANKL)and osteoprotegerin(OPG)mRNA in local bone tissue of femoral head were detected after operation,and immunohistochemical analysis was performed.Results There were no significant differences in the expressions of ACE,AngⅡ,AT1R,ACE2,Ang(1-7)and Mas-R between two groups(P>0.05).The mRNA expression levels of ACE2,Mas-R and OPG in local bone tissue of femoral head in INFH group were lower than those in control group(P<0.05),while the mRNA expression levels of ACE,AngⅡ,AT1R,RANKL and RANKL mRNA/OPG mRNA were higher in INFH group than those in control group(P<0.05).Compared with control group,HE staining of bone tissue in INFH group showed hyperplasia of adipocytes,thinning of bone trabeculae,pyknosis and deep staining of bone nucleus,and obvious increase of empty bone lacunae;Masson staining of bone tissue in INFH group showed that dark blue became lighter and more disordered,showing the decrease of collagen structure and obvious hyperplasia of fibrous structure.The results of immunohistochemistry showed that the expressions of ACE and AT1R were higher in INFH group than those in control group,while the expressions of ACE2 and Mas-R were lower than those of control group.There were significant differences in the percentage of positive expression area of ACE,AT1R,ACE2 and Mas-R between two groups(P<0.05).Conclusion Some components of RAS biaxial in local bone tissue of INFH patients are abnormally expressed,which may be involved in the process of local bone turnover and osteonecrosis,providing new ideas for the follow-up study and diagnosis and treatment.