Abstract：
BACKGROUND: Skeletal muscle ischaemia-reperfusion injury (IRI) is a prevalent condition encountered in clinical practice, characterised by muscular dystrophy. Owing to limited treatment options and poor prognosis, it can lead to movement impairments, tissue damage, and disability. This study aimed to determine and verify the influence of transient receptor potential canonical 6 (TRPC6) on skeletal muscle IRI, and to explore the role of TRPC6 in the occurrence of skeletal muscle IRI and the signal transduction pathways activated by TRPC6 to provide novel insights for the treatment and intervention of skeletal muscle IRI.
METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice.
RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R.
CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.
METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice.
RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R.
CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.
摘要：
背景：骨骼肌缺血再灌注损伤（IRI）是临床实践中遇到的普遍情况，以肌营养不良为特征。由于有限的治疗选择和不良预后，它会导致运动障碍，组织损伤,和残疾。本研究旨在确定和验证瞬时受体电位规范6（TRPC6）对骨骼肌IRI的影响，探讨TRPC6在骨骼肌IRI发生中的作用及TRPC6激活的信号转导通路，为骨骼肌IRI的治疗和干预提供新的见解。
方法：建立体内缺血/再灌注（I/R）和体外缺氧/复氧（H/R）模型，数据在组织病理学上进行了全面分析，细胞，和分子水平，以及对小鼠运动能力的评价。
结果：通过比较TRPC6基因敲除小鼠和野生型小鼠，我们发现TRPC6敲除TRPC6可以减轻I/R或H/R后骨骼肌损伤，骨骼肌，从而恢复小鼠的一些运动能力。TRPC6敲低可降低细胞内Ca2+过载，therebyo减少细胞凋亡。此外，我们还发现TRPC6不仅是参与骨骼肌IRII/R损伤的关键离子通道,但也可以影响Ca2水平，然后影响磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）信号通路。因此，通过击倒，抑制TRPC6,从而减轻骨骼肌I/R或H/R引起的损伤。
结论：这些发现数据表明，TRPC6exacerbates的存在可以加重I/Rischemia/再灌注后骨骼肌损伤的损伤，导致不仅导致Ca2+过载和细胞凋亡。,此外,它通过抑制PI3K/Akt/mTOR信号通路的表达而削弱细胞的自我修复能力。探讨TRPC6在骨骼肌中的功能和作用可能为骨骼肌缺血/再灌注损伤的治疗提供了新的方法。
方法：建立体内缺血/再灌注（I/R）和体外缺氧/复氧（H/R）模型，数据在组织病理学上进行了全面分析，细胞，和分子水平，以及对小鼠运动能力的评价。
结果：通过比较TRPC6基因敲除小鼠和野生型小鼠，我们发现TRPC6敲除TRPC6可以减轻I/R或H/R后骨骼肌损伤，骨骼肌，从而恢复小鼠的一些运动能力。TRPC6敲低可降低细胞内Ca2+过载，therebyo减少细胞凋亡。此外，我们还发现TRPC6不仅是参与骨骼肌IRII/R损伤的关键离子通道,但也可以影响Ca2水平，然后影响磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）信号通路。因此，通过击倒，抑制TRPC6,从而减轻骨骼肌I/R或H/R引起的损伤。
结论：这些发现数据表明，TRPC6exacerbates的存在可以加重I/Rischemia/再灌注后骨骼肌损伤的损伤，导致不仅导致Ca2+过载和细胞凋亡。,此外,它通过抑制PI3K/Akt/mTOR信号通路的表达而削弱细胞的自我修复能力。探讨TRPC6在骨骼肌中的功能和作用可能为骨骼肌缺血/再灌注损伤的治疗提供了新的方法。
