摘要
研究目的：本实验以电刺激跳跃法建立的末端病大鼠为研究对象,通过低功率激光照射其跟腱,从组织形态学、生物力学、生物化学、分子生物学等不同角度和层次,观察低功率激光对末端病大鼠跟腱影响的动态变化,探讨低功率激光对末端病大鼠跟腱影响及其机制,探索低功率激光在运动医学临床实践中的应用方法,为促进肌腱损伤的修复提供理论依据。
研究方法：本实验采用了电刺激跳跃法造模和激光照射法治疗。雄性Wistar大鼠96只,随机分为：空白对照组(n=8)和电刺激造模组(n=88),电刺激造模组又分为：①造模对照组(n=8)②自然愈合组(n=40),按取材时问点不同分为：1天组、2天组、3天组、7天组、14天组,每组8只。③激光照射组(n=40),按取材时间点不同分为：造模后1天照射组、2天照射组、3天照射组、7天照射组、14天照射组,每组8只。电刺激造模组的大鼠进行5周的电刺激跳跃训练之后,对激光照射组的大鼠跟腱按要求进行激光照射。测试方法与指标：①光镜HE染色和透射电镜观察大鼠跟腱内胶原纤维结构和腱细胞的变化。②Instron3365万能材料实验机测定跟腱的刚度、最大载荷等生物力学性能指标。③样本碱水解法测定跟腱内羟脯氨酸含量。④ELISA法测定跟腱内蛋白多糖、Collagen-Ⅰ、Collagen-Ⅲ、TGF-β1、MMP-1和TIMP-1的含量。⑤实时定量PCR方法测定跟腱内Collagen-Ⅰ mRNA、Collagen-Ⅲ mRNA、TGF-β1mRNA、MMP-1mRNA和TIMP-1mRNA的表达情况。
研究结果：①低功率激光照射后,HE染色光镜和透射电镜观察,胶原纤维排列趋于整齐,交联减少,腱细胞变大并逐渐增多,表明低功率激光照射能促进末端病大鼠跟腱的再生。②与自然愈合组比较,激光照射组的刚度和最大载荷在第7天开始出现了显著性差异(P<0.05)。③激光照射组与自然愈合组比较,第14天时羟脯氨酸含量出现显著性差异(P<0.05)。④经低功率激光照射后,蛋白多糖合成逐渐增加,与自然愈合组比,第7天开始出现显著性差异(P<0.05)。⑤随着时间的推移,激光照射组跟腱中胶原-I mRNA的表达逐渐增加,而胶原Ⅰ的变化出现了先小幅下降再升高的变化。激光照射组与自然愈合组的比较,在第7天出现了显著性差异(P<0.05),这种差异在第14天非常明显(P<0.01)。⑥大鼠跟腱胶原ⅢmRNA表达和胶原Ⅲ的合成量变化趋势是随时间延长而下降。激光照射组与自然愈合组相比,胶原ⅢmRNA的表达在第14天才出现明显的差异(P<0.05),而胶原Ⅲ蛋白含量在第7天就出现了显著性差异(P<0.05)。⑦随时间增加,TGF-βlmRNA的表达和TGF-β1蛋白含量缓慢下降。与自然愈合组比较,激光照射组的TGF-β1mRNA的表达和TGF-β1含量在第7天都出现了显著性差异(P<0.05)。⑧激光照射组与自然愈合组比较,MMP-1mRNA在第3天出现了显著性差异(P<0.05),直至第7、14天显著性变化都存在(P<0.05)。MMP-1蛋白的表达则在第7天才出现显著性差异(P<0.05)。⑨激光照射组与自然愈合组比较,TIMP-1mRNA的表达和TIMP-1的含量在第7天出现了显著差异(P<0.05),至14天差异变得非常明显(P<0.01)。
研究结论：①低功率激光对末端病大鼠跟腱具有治疗作用。②低功率激光通过激活腱细胞促进末端病大鼠跟腱组织的愈合。③低功率激光通过调控末端病大鼠跟腱代谢,改善其生物力学性能,从而促进跟腱的修复。④低功率激光照射能提高末端病大鼠跟腱蛋白多糖含量,减少疤痕形成,促进肌腱愈合。⑤低功率激光能使末端病大鼠跟腱羟脯氨酸含量升高,促进胶原Ⅰ的合成,加快跟腱修复。⑥低功率激光照射使末端病大鼠跟腱胶原Ⅰ和胶原Ⅲ表达增加,共同参与跟腱修复,加快末端病大鼠跟腱的早期愈合。⑦低功率激光照射可以延缓TGF-β1水平的下降,使TGF-β1保持在适宜水平,加快末端病大鼠跟腱的愈合,减少疤痕的形成。⑧低功率激光照射可调控MMP-1和TIMP-1合成代谢,下调MMP-1/TIMP-1的比值,降低胶原的降解,促进跟腱的修复。
Objective:In this experiment, electrical stimulation method was used to establish the rats model with Achilles tendon enthesiopathy.Then to observe the influence of Low power laser therapy (LLLT) from different angles and levels of tissue morphology biomechanics, biochemistry, molecular biology and so on.Discuss the mechanism of low power laser therapy on Achilles tendon enthesiopathy.Explore the application of low power laser in the clinical practice of sports medicine, to promote the restoration of tendon injuries and provide the theory basis.
Methods:The experiment adopted two kinds of model-jumping by the electricity and LPLT:96male Wistar rats were selected randomly as the control group (n=8) and the exercise group (n=88), the rats of exercise group were divided randomly into two groups again:①The exercise control group (n=8)②Nature healing group (n=40). According to the time of samples been taken, the groups were further allocated to1,2,3,7,14d after exercising. Each group has8rats.③LLLT group (n=40) LLLT groups were also allocated to1,2,3,7',14d after exercising. Each group has8rats. The rats of exercise were trained for5weeks, and then we use the LLLT on the rats of LLLT groups depending on the different needs. Text methods and Index:①Use the HE dyeing and transmission electron microscope to observe the Achilles tendon cells and change of collagen fiber structure in rats.②Instron3365universal material testing machine determines the stiffness of the Achilles tendon, maximum load and other biological mechanical performance index.③Samples alkaline hydrolysis measures the contents of hydroxyproline of the tendon.④Determining the Achilles tendon protein polysaccharide、Collagen-Ⅰ、Collagen-Ⅲ、TGF-β1MMP-1and TIMP-1content with ELISA.⑤The expression of Collagen-ImRNA、Collagen-ⅢmRNA、 TGF-β1mRNA、MMP-1mRNA and TIMP-1mRNA level were analyzed by real-time quantitative PCR technique.
Results:①After low power laser therapy, observing with HE dyeing and transmission electron microscope, found the collagen fiber arrangement tend to be neat, crosslinking reduce, tendon cells become larger and increases gradually, suggests that low power laser therapy can promote the regeneration of the Achilles tendon enthesiopathy in rats.②After7days, compared with the Natural healing group stiffness and maximum load of LLLT group began to appear the significant difference (P<0.05).③After14days, LLLT group compared with Natural healing group, hydroxyproline content appears significant difference (P<0.05).④Potein synthesis polysaccharide increase gradually after the low power laser, compared with Natural healing group, after7days it began to appear significant difference (P<0.05)⑤With the passage of time, LLLT group collagen-ImRNA expression gradually increased.The collagen-I protein initial decreased slightly and then increased.After7days the change appeared significant difference (P<0.05) and after14days the change appeared very significant difference (P<0.01) compared with the Natural healing group.⑥The mRNA and protein of collagen-III in tendon decrease with time passed by.After14days the mRNA appeared significant difference (P<0.05) compared with Natural healing group.But the significant difference of protein synthesis appeared in day7.⑦The mRNA expression and protein synthesis of TGF-β1decreased with time.After7days the mRNA and protein content in LLLT group appeared significant difference (P<0.05) compared with Natural healing group.⑧After3days the mRNA of MMP-1in LPLT group appeared significant difference (P<0.05) compared with Natural healing group, and sustained in the7th and14th day.And the significant difference (P<0.05) of protein content appeared in the7th day.⑨After7days the mRNA and protein content of TIMP-1appeared significant difference (P<0.05) and very significant difference (P<0.01) in the14th day compared with Natural healing group.
Conclusion:①Low power laser has some effects on enthesiopathy of the Achilles tendon.②Low power laser promote enthesiopathy Achilles tendon tissue recovery by activating the tendon cells.③Low power laser can regulate metabolism of rat Achilles tendon and improve the biomechanical performance, so as to promote the Achilles tendon repair.④Low power laser can upregulate the protein content of polysaccharide in rat Achilles tendon, reduce scarring and promote the tendon healing.⑤Low power laser can increase hydroxyproline content in Achilles tendon, promote collagen-I synthesis and accelerate the Achilles tendon repair.⑥Low power laser can improve collagen-Ⅰ and collagen-Ⅲ expression, participate in the Achilles tendon repair, speed up the early healing of Achilles tendon enthesiopathy.⑦Low power laser irradiation can delay TGF-β1decline, make TGF-β1keep in the appropriate level, reduce scar formation and speed up the Achilles tendon enthesiopathy healing.⑧Low power laser can balance MMP-1and TIMP-1synthesize, downregulate MMP-1/TIMP-1ratio, reduce the degradation of collagen and promote the Achilles tendon repair.
引文
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