Fang Yingyan, Guo Xiaolei, Gao Qin, Ye Hongwei, Guan Sudong
Department of Physiology, Bengbu Medical College, Bengbu, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2013 Feb;33(2):177-81.
To study the changes in diaphragmatic function and gene expressions of calcium regulatory proteins in diabetic rats and explore the mechanism of diaphragm dysfunction in diabetes mellitus.
SD rats were randomly divided into normal control group and diabetic (induced by intraperitoneal STZ injection) group. After 4 and 8 weeks, the body weight and diaphragm to body weight ratio were measured, and the activities of succinic dehydrogenase (SDH) in the diaphragm and blood glucose were assayed. The diaphragm contractility was assessed and the alterations of diaphragm ultrastructure were observed. RT-PCR was used to detect the changes in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLB) mRNA expressions in the diaphragm.
The diabetic rats showed a significant weight loss with a lowered diaphragm to body weight ratio (P<0.01) and SDH activity (P<0.01). The peak twitch tension and maximum tetanic tension of the diaphragm were significantly lowered and the time to peak contraction and half relaxation time significantly prolonged (P<0.01) in the diabetic rats, which also exhibited a lowered tetanic force in response to stimulus (P<0.01). Transmission electron microscopy revealed obvious ultrastructural changes of the diaphragm in diabetic rats. RT-PCR showed significantly decreased SERCA and increased PLB mRNA expressions in diabetic rat diaphragm (P<0.01), and these changes intensified with time (P<0.01).
Diabetes can cause impairment of diaphragmatic ultrastructure, mitochondrial injuries, and lowered SDH activity and ATP production. Decreased SERCA and increased PLB mRNA expressions in diabetes result in reduced Ca(2+) uptake by the diaphragm sarcoplasmic reticulum to induce diaphragm dysfunction.
研究糖尿病大鼠膈肌功能及钙调节蛋白基因表达的变化，探讨糖尿病膈肌功能障碍的机制。
将SD大鼠随机分为正常对照组和糖尿病组（腹腔注射链脲佐菌素诱导）。4周和8周后，测量体重和膈肌与体重比，检测膈肌琥珀酸脱氢酶（SDH）活性和血糖。评估膈肌收缩力并观察膈肌超微结构的改变。采用逆转录聚合酶链反应（RT-PCR）检测膈肌肌浆网Ca(2+)-ATP酶（SERCA）和受磷蛋白（PLB）mRNA表达的变化。
糖尿病大鼠体重显著减轻，膈肌与体重比降低（P<0.01），SDH活性降低（P<0.01）。糖尿病大鼠膈肌的单收缩峰值张力和最大强直张力显著降低，收缩达峰时间和半舒张时间显著延长（P<0.01），对刺激的强直收缩力也降低（P<0.01）。透射电子显微镜显示糖尿病大鼠膈肌有明显的超微结构改变。RT-PCR显示糖尿病大鼠膈肌SERCA mRNA表达显著降低，PLB mRNA表达增加（P<0.01），且这些变化随时间加剧（P<0.01）。
糖尿病可导致膈肌超微结构损伤、线粒体损伤，SDH活性降低和ATP生成减少。糖尿病时SERCA降低和PLB mRNA表达增加导致膈肌肌浆网Ca(2+)摄取减少，从而引起膈肌功能障碍。
