Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, China.
Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, China; The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Biomed Pharmacother. 2017 Dec;96:513-523. doi: 10.1016/j.biopha.2017.10.012. Epub 2017 Oct 13.
Previous studies in our lab have shown that tetramethylpyrazine (TMP) could effectively attenuate disuse induced muscle atrophy. In order to screening out the optimal dose of tetramethylpyrazine (TMP) for protection against disuse induced muscle atrophy in hindlimb unloading (HLU) rats, in this study, we compared effects of 4 TMP doses on muscle wet weight (MWW), the ratios of muscle wet weight/body weight (MWW/BW) and muscle wet weight/dry weight (MWW/DW), fiber type composition, as well as cross-sectional area (CSA) in soleus (SOL) muscle. Consequently, we quantified optimal dose effects on both functional properties and protein expression (calpain-1, calpain-2, calpastatin and MuRF1) in SOL and extensor digitorum longus (EDL) muscles. Data indicated that the protective potential of TMP was dose-dependent: 60mg/kg TMP was most effective in terms of atrophy prevention. This dose reduced SOL MWW, MWW/BW and CSA muscle loss by 60, 60 and 54% (P<0.001), respectively. HLU-induced slow-to-fast fiber transition was reduced by 17% (P<0.01). 60mg/kg TMP also significantly lessened the decrease of contractile force, the increase of shorting velocity and fatigability induced by HLU. Besides, it also attenuated expressions of calpain-1 (SOL -8.6%, P<0.05; EDL -10.9%, P<0.05), calpain-2 (SOL -60%, P<0.001; EDL -32%, P<0.01) and MuRF1 expression (SOL -21%, P<0.001; EDL -10%, P<0.01), promoted the expression of calpastatin by 18% (P<0.05) in SOL muscle. Taken together, present study demonstrated that 60mg/kg body weight was the optimal dose of TMP against disuse induced muscle atrophy which effectively protected muscle function by inhibiting calpain-1, calpain-2 and MuRF1 expression, promoted calpastatin expression, especially in slow-twitch muscle.
先前我们实验室的研究表明，川芎嗪（TMP）可有效减轻废用性肌肉萎缩。为了筛选出四甲基吡嗪（TMP）对后肢去负荷（HLU）大鼠废用性肌肉萎缩的最佳保护剂量，本研究比较了 4 种 TMP 剂量对比目鱼肌湿重（MWW）、肌肉湿重/体重（MWW/BW）和肌肉湿重/干重（MWW/DW）比值、纤维类型组成以及比目鱼肌（SOL）肌横截面积（CSA）的影响。因此，我们量化了 TMP 对 SOL 和伸趾长肌（EDL）肌肉功能特性和蛋白质表达（钙蛋白酶-1、钙蛋白酶-2、钙蛋白酶抑制剂和 MuRF1）的最佳剂量效应。数据表明，TMP 的保护潜力与剂量呈正相关：60mg/kg TMP 对预防萎缩最有效。该剂量可使 SOL MWW、MWW/BW 和 CSA 肌肉损失分别减少 60%、60%和 54%（P<0.001）。HLU 诱导的慢肌向快肌纤维的转变减少了 17%（P<0.01）。60mg/kg TMP 还显著减少了 HLU 引起的收缩力下降、缩短速度增加和易疲劳性。此外，它还能减弱钙蛋白酶-1（SOL-8.6%，P<0.05；EDL-10.9%，P<0.05）、钙蛋白酶-2（SOL-60%，P<0.001；EDL-32%，P<0.01）和 MuRF1 表达（SOL-21%，P<0.001；EDL-10%，P<0.01），促进钙蛋白酶抑制剂的表达增加 18%（P<0.05）。综上所述，本研究表明，60mg/kg 体重是 TMP 对抗废用性肌肉萎缩的最佳剂量，它通过抑制钙蛋白酶-1、钙蛋白酶-2 和 MuRF1 的表达有效保护肌肉功能，促进钙蛋白酶抑制剂的表达，特别是在慢肌中。
