Sarcopenia associated with portosystemic shunting is reversed by follistatin.
Sarcopenia associated with portosystemic shunting is reversed by follistatin.
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DOI：
10.1016/j.jhep.2010.08.032
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发表时间：
2011-05
影响因子：
25.7
通讯作者：
Kalhan SC
中科院分区：
文献类型：
--
作者：
Dasarathy S;McCullough AJ;Muc S;Schneyer A;Bennett CD;Dodig M;Kalhan SC
门体分流术（PSS）在肝硬化常见的肌肉减少症（骨骼肌损失）发病机制中的独特作用尚不清楚。我们先前已经表明，在门腔静脉吻合（PCA）的PSS肌肉减少症大鼠模型中，肌肉生长抑制素（骨骼肌质量抑制剂）的表达增加。本研究旨在探讨PCA后肌肉减少症的发生机制。在PCA和假手术配对喂养对照大鼠中，使用苯丙氨酸淹没剂量法来定量骨骼肌中随时间推移和响应于卵泡抑素（一种肌生长抑制素拮抗剂）的蛋白质合成率分数和绝对值。通过实时PCR和Western blot分析定量肌生长抑制素和卫星细胞（肌细胞前体）增殖和分化的标志物的表达。与对照组大鼠相比，PCA组大鼠骨骼肌蛋白的绝对合成率（ASR）在第2、4和6周时均较低（p <0.05），而骨骼肌蛋白的部分合成率（FSR）在第2周时显著较低（p <0.05）。PCA后4周和6周，肌生长抑制素表达升高，而卫星细胞增殖和分化标志物降低。卵泡抑素增加骨骼肌质量，肌肉FSR和ASR，降低肌生长抑制素蛋白的表达，并增加卫星细胞功能标志物的表达。与PSS相关的肌肉减少症是由蛋白质合成受损和肌生长抑制素表达增加导致的卫星细胞功能降低引起的。在人类肝硬化患者中证实这些改变将为肝病的肌肉减少症提供新的治疗靶点。
The distinct role of portosystemic shunting (PSS) in the pathogenesis of sarcopenia (skeletal muscle loss) that occurs commonly in cirrhosis is unclear. We have previously shown increased expression of myostatin (inhibitor of skeletal muscle mass) in the portacaval anastamosis (PCA) rat model of sarcopenia of PSS. The present study was performed to examine the mechanisms of sarcopenia following PCA. In PCA and sham operated pair fed control rats, the phenylalanine flooding dose method was used to quantify the fractional and absolute protein synthesis rates in the skeletal muscle over time and in response to follistatin, a myostatin antagonist. The expression of myostatin and markers of satellite cell (myocyte precursors) proliferation and differentiation were quantified by real-time PCR and Western blot analyses. The absolute synthesis rate (ASR) was lower at 2, 4, and 6 weeks (p <0.05) and the fractional synthesis rate (FSR) of skeletal muscle protein was significantly lower (p <0.05) at week 2 in the PCA rats compared to control rats. Expression of myostatin was elevated while markers of satellite cell proliferation and differentiation were lower at 4 and 6 weeks after PCA. Follistatin increased skeletal muscle mass, muscle FSR and ASR, decreased expression of myostatin protein, and an increased expression of markers of satellite cell function. Sarcopenia associated with PSS is caused by impaired protein synthesis and reduced satellite cell function due to increased myostatin expression. Confirming these alterations in human patients with cirrhosis will provide novel therapeutic targets for sarcopenia of liver disease.
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影响因子：
4.8
作者：
Hill, JJ;Davies, MV;Qiu, YC
通讯作者：
Qiu, YC
DOI：
10.1152/ajpgi.00080.2005
发表时间：
2006-01-01
影响因子：
4.5
作者：
Patella, S;Phillips, DJ;Sievert, W
通讯作者：
Sievert, W
DOI：
10.1152/ajpendo.00433.2005
发表时间：
2006-03-01
影响因子：
5.1
作者：
Welle, S;Bhatt, K;Pinkert, CA
通讯作者：
Pinkert, CA
影响因子：
7.8
作者：
McCroskery, Seumas;Thomas, Mark;Maxwell, Linda;Sharma, Mridula;Kambadur, Ravi
通讯作者：
Kambadur, Ravi
影响因子：
3.7
作者：
Lee, Se-Jin
通讯作者：
Lee, Se-Jin