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[1]田佳慶,劉良燕,彭鵬,等.基于“成骨-成血管”理論探討全身振動(dòng)療法治療激素性股骨頭壞死的效果及作用機(jī)制[J].中醫(yī)正骨,2024,36(09):59-68,82.
　TIAN Jiaqing,LIU Liangyan,PENG Peng,et al.Efficacy and mechanism of whole body vibration therapy in treatment of steroid-induced osteonecrosis of the femoral head:a osteogenesis-angiogenesis theory-based experimental study[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2024,36(09):59-68,82.
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基于“成骨-成血管”理論探討全身振動(dòng)療法治療激素性股骨頭壞死的效果及作用機(jī)制()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第36卷
期數(shù):
2024年09期
頁碼:
59-68,82
欄目:
技術(shù)研究
出版日期:
2024-09-20

文章信息/Info

Title:
Efficacy and mechanism of whole body vibration therapy in treatment of steroid-induced osteonecrosis of the femoral head:a osteogenesis-angiogenesis theory-based experimental study
作者:
田佳慶1; 劉良燕2; 彭鵬1; 林錕1; 陸舜1; 何憲順1; 魏騰飛1; 何敏聰3; 欽逸仙4; 何偉3; 魏秋實(shí)3
(1.廣州中醫(yī)藥大學(xué)第三臨床醫(yī)學(xué)院,廣東 廣州 510006; 2.揭西縣中醫(yī)醫(yī)院,廣東 揭西 515400; 3.廣州中醫(yī)藥大學(xué)第三附屬醫(yī)院,廣東 廣州 510378; 4.紐約州立大學(xué)石溪分校,紐約 11794-5281)
Author(s):
TIAN Jiaqing1; LIU Liangyan2; PENG Peng1; LIN Kun1; LU Shun1; HE Xianshun1; WEI Tengfei1; HE Mincong3; QIN Yixian4; HE Wei3; WEI Qiushi3
1.The Third Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510006,Guangdong,China 2.Jiexi Hospital of Traditional Chinese Medicine,Jiexi 515400,Guangdong,China 3.The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510378,Guangdong,China 4.State University of New York at Stony Brook,New York 11794-5281,USA
關(guān)鍵詞:
股骨頭壞死;  糖皮質(zhì)激素;  全身振動(dòng)療法;  骨生成;  血管生成;  H型血管;  Piezo1蛋白
Keywords:
femur head necrosis;  glucocorticoids;  whole body vibration therapy;  osteogenesis;  angiogenesis;  type H blood vessels;  Piezo1 protein
摘要:
目的:觀察全身振動(dòng)療法(whole body vibration therapy,WBVT)治療激素性股骨頭壞死(steroid-induced osteonecrosis of the femoral head,SONFH)的效果,并探討其治療SONFH的作用機(jī)制。方法:將50只SD大鼠隨機(jī)分為空白組、模型組、WBVT組、Yoda1組、WBVT聯(lián)合蜘蛛毒液肽(Grammostola spatulata mechanotoxin 4,GsMTx4)組。模型組、WBVT組、Yoda1組、WBVT聯(lián)合GsMTx4組大鼠采用脂多糖聯(lián)合甲潑尼龍琥珀酸鈉構(gòu)建SONFH模型。造模后,WBVT組使用WBVT干預(yù),Yoda1組使用Piezo1蛋白激動(dòng)劑Yoda1干預(yù),WBVT聯(lián)合GsMTx4組使用WBVT和Piezo1蛋白抑制劑GsMTx4干預(yù)。干預(yù)結(jié)束后,進(jìn)行大鼠股骨頭組織病理學(xué)觀察(計(jì)算股骨頭空骨陷窩率)、骨微結(jié)構(gòu)觀察,以及股骨頭內(nèi)Piezo1、骨形態(tài)發(fā)生蛋白2(bone morphogenetic protein 2,BMP2)、Runt相關(guān)轉(zhuǎn)錄因子2(Runt-related transcription factor 2,Runx2)、低氧誘導(dǎo)因子-1α(hypoxia-inducible factor-1α,HIF-1α)、血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor,VEGF)、分化簇31(cluster of differentiation 31,CD31)/內(nèi)皮粘蛋白(endomucin,EMCN)蛋白表達(dá)量檢測(cè)。結(jié)果:①大鼠股骨頭組織病理學(xué)觀察結(jié)果。空白組大鼠的股骨頭內(nèi)骨小梁致密且排列整齊。與空白組相比,模型組大鼠股骨頭內(nèi)的骨小梁較為稀疏,骨小梁細(xì)小、不連續(xù),且排列紊亂。與模型組相比,WBVT組和Yoda1組大鼠的股骨頭內(nèi)骨小梁數(shù)量增多,排列較為整齊。與WBVT組相比,WBVT聯(lián)合GsMTx4組大鼠的股骨頭內(nèi)骨小梁排列則較為紊亂。模型組、WBVT組、Yoda1組、WBVT聯(lián)合GsMTx4組大鼠的股骨頭空骨陷窩率均高于空白組(P=0.000,P=0.000,P=0.000,P=0.000),WBVT組、Yoda1組大鼠的股骨頭空骨陷窩率均低于模型組(P=0.000,P=0.000),WBVT聯(lián)合GsMTx4組大鼠的股骨頭空骨陷窩率高于WBVT組(P=0.000)。②大鼠股骨頭骨微結(jié)構(gòu)觀察結(jié)果。WBVT組和Yoda1組大鼠的股骨頭骨體積分?jǐn)?shù)、骨小梁厚度、骨小梁數(shù)量、骨小梁分離度與空白組的差異均無統(tǒng)計(jì)學(xué)意義(P=0.213,P=0.081,P=0.384,P=0.471; P=0.435,P=0.131,P=0.104,P=0.126)。模型組和WBVT聯(lián)合GsMTx4組大鼠的股骨頭骨體積分?jǐn)?shù)、骨小梁厚度、骨小梁數(shù)量均低于空白組(P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000),骨小梁分離度均高于空白組(P=0.000,P=0.000)。WBVT組和Yoda1組大鼠的股骨頭骨體積分?jǐn)?shù)、骨小梁厚度、骨小梁數(shù)量均高于模型組(P=0.000,P=0.002,P=0.000; P=0.000,P=0.007,P=0.014),骨小梁分離度均低于模型組(P=0.000,P=0.000)。WBVT組大鼠的股骨頭骨體積分?jǐn)?shù)、骨小梁厚度、骨小梁數(shù)量、骨小梁分離度與Yoda1組的差異均無統(tǒng)計(jì)學(xué)意義(P=0.194,P=0.223,P=0.332,P=0.071)。WBVT聯(lián)合GsMTx4組大鼠的股骨頭骨體積分?jǐn)?shù)、骨小梁厚度、骨小梁數(shù)量均低于WBVT組(P=0.002,P=0.021,P=0.000),骨小梁分離度高于WBVT組(P=0.000)。③大鼠股骨頭內(nèi)Piezo1、BMP2、Runx2、HIF-1α、VEGF蛋白表達(dá)量檢測(cè)結(jié)果。WBVT組和Yoda1組大鼠股骨頭內(nèi)Piezo1、BMP2、Runx2、HIF-1α、VEGF蛋白表達(dá)量與空白組的差異均無統(tǒng)計(jì)學(xué)意義(P=0.061,P=0.122,P=0.773,P=0.814,P=0.991; P=0.112,P=0.071,P=0.955,P=0.749,P=0.915)。模型組和WBVT聯(lián)合GsMTx4組大鼠股骨頭內(nèi)Piezo1、BMP2、Runx2、HIF-1α、VEGF蛋白表達(dá)量均低于空白組(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000,P=0.000,P=0.000)。WBVT組和Yoda1組大鼠股骨頭內(nèi)Piezo1、BMP2、Runx2、HIF-1α、VEGF蛋白表達(dá)量均高于模型組(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000,P=0.000,P=0.000)。WBVT組大鼠股骨頭內(nèi)Piezo1、BMP2、Runx2、HIF-1α、VEGF蛋白表達(dá)量與Yoda1組的差異均無統(tǒng)計(jì)學(xué)意義(P=0.962,P=0.179,P=0.214,P=0.990,P=0.975)。WBVT聯(lián)合GsMTx4組大鼠股骨頭內(nèi)Piezo1、BMP2、Runx2、HIF-1α、VEGF蛋白表達(dá)量均低于WBVT組(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000)。④大鼠股骨頭內(nèi)CD31/EMCN蛋白表達(dá)量檢測(cè)結(jié)果。模型組和WBVT聯(lián)合GsMTx4組大鼠股骨頭內(nèi)CD31/EMCN表達(dá)量均低于空白組(P=0.000,P=0.000)。WBVT組和Yoda1組大鼠股骨頭內(nèi)CD31/EMCN表達(dá)量與空白組的差異均無統(tǒng)計(jì)學(xué)意義(P=0.412,P=0.991)。WBVT組和Yoda1組大鼠股骨頭內(nèi)CD31/EMCN表達(dá)量均高于模型組(P=0.000,P=0.000)。WBVT聯(lián)合GsMTx4組大鼠股骨頭內(nèi)CD31/EMCN表達(dá)量低于WBVT組(P=0.000)。結(jié)論:WBVT可以促進(jìn)股骨頭壞死組織修復(fù),其作用機(jī)制可能與上調(diào)Piezo1蛋白的表達(dá)影響HIF-1α/VEGF軸,進(jìn)而促進(jìn)股骨頭內(nèi)H型血管的生成、改善股骨頭血供有關(guān)。
Abstract:
Objective:To observe the outcomes of whole body vibration therapy(WBVT)in treatment of steroid-induced osteonecrosis of the femoral head(SONFH),and to explore its underlying mechanism.Methods:Fifty Sprague-Dawley(SD)rats were randomized into blank group,model group,WBVT group,Yoda1 group,WBVT combined Grammostola spatulata mechanotoxin 4(GsMTx4)group.The rats in model group,WBVT group,Yoda1 group,WBVT combined GsMTx4 group were intervened by lipopolysaccharide and methylprednisolone sodium succinate for inducing SONFH.After successful modeling,the rats in WBVT group,Yoda1 group and WBVT combined GsMTx4 group were further intervened with WBVT,Yoda1(a Piezo1 agonist),as well as WBVT and GsMTx4(a Piezo1 inhibitor),respectively.After the end of intervention,the histopathological changes of the femur head were observed and the percentage of empty lacunae in femur head were calculated; meanwhile,the bone microstructure of the femur head was observed and analyzed; furthermore,the protein expression levels of Piezo1,bone morphogenetic protein 2(BMP2),Runt-related transcription factor 2(Runx2),hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),and cluster of differentiation 31(CD31)/endomucin(EMCN)in femur head were detected.Results:①The results of observation on histopathological changes in femur head tissues of rats.In rats from blank group,the dense and well-arranged trabeculae were found within the femur heads; compared with that of blank group,the sparse,small,discontinuous and disordered arranged trabeculae were presented within the femur heads in rats of model group; compared with that of model group,the trabeculae increased and relatively neatly arranged within the femur heads in rats of WBVT group and Yoda1 group; whereas,compared with that of WBVT group,the trabeculae disorderedly arranged within the femur heads in rats of WBVT combined GsMTx4 group.Besides,the percentage of empty lacunae in femur head was higher in model group,WBVT group,Yoda1 group,WBVT combined GsMTx4 group compared to blank group(P=0.000,P=0.000,P=0.000,P=0.000),and was higher in model group compared to WBVT group and Yoda1 group(P=0.000,P=0.000),and was higher in WBVT combined GsMTx4 group compared to WBVT group(P=0.000).②The results of observation on bone microstructure of femur head in rats.The differences were not statistically significant in bone volume fraction(BVF),trabecular thickness(Tb.Th),trabecular number(Tb.N),and trabecular separation(Tb.Sp)of femur head between WBVT group and blank group,as well as between Yoda1 group and blank group(P=0.213,P=0.081,P=0.384,P=0.471; P=0.435,P=0.131,P=0.104,P=0.126).The BVF and Tb.Th were smaller,the Tb.N was fewer,while,the Tb.Sp was greater in model group and WBVT combined GsMTx4 group compared to blank group(P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000; P=0.000,P=0.000).The BVF and Tb.Th were greater,the Tb.N was more,while,the Tb.Sp was smaller in WBVT group and Yoda1 group compared to model group(P=0.000,P=0.002,P=0.000; P=0.000,P=0.007,P=0.014; P=0.000,P=0.000); while,the comparisons between WBVT group and Yoda1 group revealed no significant differences(P=0.194,P=0.223,P=0.332,P=0.071).Additionally,the BVF and Tb.Th were smaller,the Tb.N was fewer,while,the Tb.Sp was greater in WBVT combined GsMTx4 group compared to WBVT group(P=0.002,P=0.021,P=0.000,P=0.000).③The results of detection on the protein expression levels of Piezo1,BMP2,Runx2,HIF-1α and VEGF in femur head of rats.The differences were not statistically significant in the protein expression levels of Piezo1,BMP2,Runx2,HIF-1α and VEGF in femur head of rats between WBVT group and Yoda1 group(P=0.061,P=0.122,P=0.773,P=0.814,P=0.991; P=0.112,P=0.071,P=0.955,P=0.749,P=0.915); while,the protein expression levels of Piezo1,BMP2,Runx2,HIF-1α and VEGF in femur head of rats were lower in model group and WBVT combined GsMTx4 group compared to blank group(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000,P=0.000,P=0.000).The protein expression levels of Piezo1,BMP2,Runx2,HIF-1α and VEGF in femur head of rats were higher in WBVT group and Yoda1 group compared to model group(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000,P=0.000,P=0.000),while,the comparison between WBVT group and Yoda1 group revealed no significant differences(P=0.962,P=0.179,P=0.214,P=0.990,P=0.975).Additionally,the protein expression levels of Piezo1,BMP2,Runx2,HIF-1α and VEGF in femur head of rats were lower in WBVT combined GsMTx4 group compared to WBVT group(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000).④The results of detection on the protein expression level of CD31/EMCN in femur head of rats.The protein expression level of CD31/EMCN in femur head of rats was lower in model group and WBVT combined GsMTx4 group compared to blank group(P=0.000,P=0.000),while,the comparisons between WBVT group and blank group,as well as between Yoda1 group and blank group revealed no significant differences(P=0.412,P=0.991).The protein expression level of CD31/EMCN in femur head of rats was higher in WBVT group and Yoda1 group compared to model group(P=0.000,P=0.000),while,was lower in WBVT combined GsMTx4 group compared to WBVT group(P=0.000).Conclusion:WBVT can promote the repair of necrotic tissues in femur head.It may work by affecting the HIF-1α/VEGF axis through up-regulating the expression of Piezo1 protein,thereby promoting the formation of type H blood vessels in femur head and improving the blood supply to the femur head.

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備注/Memo

備注/Memo:
基金項(xiàng)目:國家自然科學(xué)基金項(xiàng)目(82274544,82004392); 廣東省基礎(chǔ)與應(yīng)用基礎(chǔ)研究基金項(xiàng)目(2023A1515010551); 廣東省中醫(yī)骨傷研究院開放課題重點(diǎn)項(xiàng)目(GYH202101-01,GYH202101-04)
通訊作者:魏秋實(shí) E-mail:[email protected]
更新日期/Last Update: 1900-01-01