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過度表現熱休克蛋白質72減緩耗竭性運動所誘發的傷害

Decrease of Exhaustive Exercise-Induced Damage by Overexpression of Heat Shock Protein 72

摘要


終生表現在骨骼肌的熱休克蛋白質72(heat shock protein 72;HSP72)已被認為可對抗老化所引起的氧化壓力及肌肉傷害。本研究目的在探討耗竭性運動所引起的受傷可否被全身終生表現的HSP72所保護。本研究所使用的方法是將帶有異核基因結合子的豬HSP70.2基因轉殖鼠([+]HSP72)和不帶豬HSP70.2基因的基因轉殖鼠([-]HSP72)置於一誘導運動性衰竭的模式;老鼠分四組:分別是控制組、HSP72組、耗竭運動組及HSP72耗竭運動組。且動物在經耗竭性運動誘導82分鐘後測定腦、心、肝、肺、腎及股四頭肌HSP72的表現、肌肉基質金屬蛋白酶活性、病理切片判讀及P-38有絲分裂活化蛋白質激酶的表現。實驗結果顯示:耗竭運動組及HSP72耗竭運動組其耗竭反應潛伏期平均分別是是82分及110分,即HSP72耗竭運動組有較長的耗竭運動時間;故本研究將耗竭運動生成時間(即開始進行誘發耗竭運動至動物完全不再運動的時間平均值)定義為耗竭反應潛伏期,且為82分鐘;HSP72耗竭運動組比耗竭運動組在耗竭性運動生成後有較低的基質金屬蛋白酶活性、較不嚴重的病理型態傷害及較高的磷酸化有絲分裂活化蛋白質激酶的表現。本研究結論為過度表現HSP72可改善運動耗竭模式的發炎及傷害,此結果可能與組織磷酸化有絲分裂活化蛋白質激酶的表現有關。

並列摘要


Lifelong overexpression of heat shock protein (HSP) 72 in skeletal muscle is known to protect against age-related oxidative stress and muscle damage. This study aimed to ascertain whether exhaustive exercise-induced damage can be prevented by lifelong overexpression of HSP72. Transgenic mice that were heterozygous for a porcine HSP70.2 gene ([+]HSP72) and transgene-negative littermate controls ([-]HSP72) were subjected to an exhaustive exercise protocol. Mice were divided into four groups, including control, HSP72, exhaustive exercise and HSP72 exhaustive exercise groups. Eighty-two min after completion of the exhaustive exercise, animals were sacrificed and different tissues, including brain, heart, liver, lung, kidney and muscle were isolated. Then the levels of HSP72, matrix metalloproteinase (an indicator for inflammatory myopathies), pathological observations and p-P-38 MAP kinase (p-P-38) expressions were determined in all tissues. When exhaustive exercise group or HSP72 exhaustive exercise group underwent an exhaustive exercise test, the latency values (the mean duration of exhaustive exercise onset) for the occurrence of exhaustive exercise was found to be different significantly (82 ± 3 and 110 ± 3 min, respectively). HSP72 exhaustive exercise group underwent a exhaustive exercise test, and had a longer exercise time. Furthermore HSP72 exhaustive exercise group showed significantly increased matrix metalloproteinase levels and p-P-38 expression, whereas morphological damage was significantly decreased compared to exhaustive exercise group. The results suggest that the improvement of inflammation and damage induced by exhaustive exercise in HSP72 overexpressing transgenic mice may be associated with p-P-38 expression.

參考文獻


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