[Experimental study on losartan decreasing denervated skeletal muscle atrophy through reducing cell apoptosis].
OBJECTIVE
To explore the role of cell apoptosis in denervated skeletal muscle atrophy in rats and the effect of losartan on it.


METHODS
Forty-two Sprague Dawley rats were randomly divided into 3 groups: group I (n = 14, normal control group), group II (n = 14, denervated group) and group III (n = 14, losartan group). The rats were not treated in group I, and were made denervated gastrocnemius models in groups II and III. In group III, the rats were treated with losartan 10 mg/kg x d by gavage and with normal saline in groups I and II. After 4 weeks, gastrocnemius mass to body mass ratio (GAS/BM) served as the degree of muscle atrophy. Apoptotic cells in gastrocnemius were stained in situ by using TUNEL. Gastrocnemius Bcl-2 and Bax protein were quantified by immunohistochemistry and Western blot. Bax/Bcl-2 served as the degree of apoptosis.


RESULTS
The ratio of apoptosis was higher in group II than that in group I (11.32% +/- 4.51% vs 0.56% +/- 0.21%, P < 0.05). The ratio of apoptosis was lower in group III than that in group II (7.21% +/- 2.05% vs 11.32% +/- 4.51%, P < 0.05). The atrophy of skeletal muscle (GAS/BM) in group II was more serious than that in group I (11.68 +/- 1.98 vs 12.86 +/- 0.74, P < 0.05), there was no significant difference between group III and group II (12.11 +/- 0.65 vs 11.68 +/- 1.98, P > 0.05). The expression of Bcl-2 in group II (18.3% +/- 4.9%) was significantly lower than that in group I (27.5% +/- 2.8%) and group III (25.5% +/- 3.5%); there was no significant difference between group III and group I (P > 0.05). The expression of Bax in group II (24.1% +/- 3.1%) was significantly higher than that in group I (22.1% +/- 3.6%) and group III (21.7% +/- 2.3%); there was no significant difference between group III and group I (P > 0.05). Western blot results showed that: the expressions of Bcl-2 were 122.5 +/- 14.6 in group II, 135.3 +/- 6.2 in group I and 139.2 +/- 16.2 in group III; showing significant differences between group II and group I, between group III and group II (P < 0.05). The expressions of Bax were 107.1 +/- 15.8 in group II, 89.3 +/- 8.4 in group I, and 94.2 +/- 9.5 in group III; showing significant differences between group II and group I, between group III and group II (P < 0.05). There was no significant difference in the expression of Bcl-2 and Bax between group III and group I (P > 0.05).


CONCLUSIONS
Cell apoptosis plays an important role in denervated skeletal muscle atrophy in rats and may be one of the factors causing skeletal muscle atrophy. Losartan can decrease skeletal muscle cell apoptosis through regulating the ratio of Bax/Bcl-2.
Tian
Feng
F
Department of Hand and Foot Surgery, Shengjing Hospital of China Medical University, Shenyang Liaoning, 110004, P.R. China. tianfeng2002@sina.com
Tian
Lijie
L
Wang
Bin
B
Ji
Xianglu
X
Bai
Zhe
Z
Wang
Fei
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009133:Muscular Atrophy / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019808:Losartan