卵巢功能丧失导致关节炎大鼠骨骼肌损失增加。
Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats.
作者信息
Furlanetto Júnior Roberto, Martins Fernanda Maria, Oliveira Anselmo Alves de, Nunes Paulo Ricardo Prado, Michelin Márcia Antoniazi, Murta Eddie Fernando Candido, Orsatti Fábio Lera
机构信息
Exercise Biology Research Group (BioEx), Health Sciences Institute, Universidade Federal do Triângulo Mineiro (UFTM), Uberaba, Minas Gerais, Brazil.
Research Institute of Oncology (IPON), Discipline of Gynecology and Obstetrics, UFTM, Uberaba, Minas Gerais, Brazil.
出版信息
Rev Bras Ginecol Obstet. 2016 Feb;38(2):56-64. doi: 10.1055/s-0035-1571265. Epub 2016 Feb 2.
OBJECTIVE
We studied the effects of loss of ovarian function (ovariectomy) on muscle mass of gastrocnemius and the mRNA levels of IGF-1, atrogin-1, MuRF-1, and myostatin in an experimental model of rheumatoid arthritis in rats.
METHODS
We randomly allocated 24 female Wistar rats (9 weeks, 195.3 ± 17.4 grams) into four groups: control (CT-Sham; n = 6); rheumatoid arthritis (RA; n = 6); ovariectomy without rheumatoid arthritis (OV; n = 6); ovariectomy with rheumatoid arthritis (RAOV; n = 6). We performed the ovariectomy (OV and RAOV) or Sham (CT-Sham or RA) procedures at the same time, fifteen days before the rheumatoid arthritis induction. The RA and RAOV groups were immunized and then were injected with Met-BSA in the tibiotarsal joint. After 15 days of intra-articular injections the animals were euthanized. We evaluated the external manifestations of rheumatoid arthritis (perimeter joint) as well as animal weight, and food intake throughout the study. We also analyzed the cross-sectional areas (CSA) of gastrocnemius muscle fibers in 200 fibers (H&E method). In the gastrocnemius muscle, we analyzed mRNA expression by quantitative real time PCR followed by the Livak method (ΔΔCT).
RESULTS
The rheumatoid arthritis induced reduction in CSA of gastrocnemius muscle fibers. The RAOV group showed a lower CSA of gastrocnemius muscle fibers compared to RA and CT-Sham groups. Skeletal muscle IGF-1 mRNA increased in arthritics and ovariectomized rats. The increased IGF-1 mRNA was higher in OV groups than in the RA and RAOV groups. Antrogin-1 mRNA also increased in the gastrocnemius muscle of arthritic and ovariectomized rats. However, the increased atrogin-1 mRNA was higher in RAOV groups than in the RA and OV groups. Gastrocnemius muscle MuRF-1 mRNA increased in the OV and RAOV groups, but not in the RA and Sham groups. However, the RAOV group showed higher MuRF-1 mRNA than the OV group. The myostatin gene expression was similar in all groups.
CONCLUSION
Loss of ovarian function results in increased loss of skeletal muscle-related ubiquitin ligases atrogin-1 and MuRF-1 in arthritic rats.
目的
在大鼠类风湿性关节炎实验模型中，我们研究了卵巢功能丧失（卵巢切除术）对腓肠肌肌肉质量以及胰岛素样生长因子-1（IGF-1）、肌肉萎缩相关蛋白-1（atrogin-1）、肌肉特异性泛素连接酶-1（MuRF-1）和肌抑素mRNA水平的影响。
方法
我们将24只雌性Wistar大鼠（9周龄，体重195.3±17.4克）随机分为四组：对照组（CT-Sham；n = 6）；类风湿性关节炎组（RA；n = 6）；无类风湿性关节炎的卵巢切除组（OV；n = 6）；患类风湿性关节炎的卵巢切除组（RAOV；n = 6）。在诱导类风湿性关节炎前15天，我们同时进行卵巢切除术（OV和RAOV组）或假手术（CT-Sham或RA组）。RA组和RAOV组先进行免疫，然后在胫跗关节注射甲硫氨酸-牛血清白蛋白（Met-BSA）。关节内注射15天后，将动物安乐死。在整个研究过程中，我们评估了类风湿性关节炎的外在表现（关节周长）以及动物体重和食物摄入量。我们还采用苏木精-伊红（H&E）染色法分析了200条腓肠肌纤维的横截面积（CSA）。在腓肠肌中，我们采用实时定量聚合酶链反应（qRT-PCR）结合Livak法（ΔΔCT）分析mRNA表达。
结果
类风湿性关节炎导致腓肠肌纤维CSA减小。与RA组和CT-Sham组相比，RAOV组腓肠肌纤维CSA更低。关节炎大鼠和卵巢切除大鼠的骨骼肌IGF-1 mRNA增加。OV组中IGF-1 mRNA的增加高于RA组和RAOV组。atrogin-1 mRNA在关节炎大鼠和卵巢切除大鼠的腓肠肌中也增加。然而，RAOV组中atrogin-1 mRNA的增加高于RA组和OV组。OV组和RAOV组的腓肠肌MuRF-1 mRNA增加，而RA组和假手术组未增加。然而，RAOV组的MuRF-1 mRNA高于OV组。所有组的肌抑素基因表达相似。
结论
卵巢功能丧失导致关节炎大鼠骨骼肌相关泛素连接酶atrogin-1和MuRF-1的丢失增加。
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