The Research Of The Effects Of TWEAK In Quadriceps Femoris Muscle Fiber-type Transformation Of COPD

Objective:This study was designed to further characterize quadriceps femoris muscle alterations in rats with chronic obstructive pulmonary disease (COPD) and to evaluate the possible relationship between Tumor necrosis factor like weak inducer of apoptosis (TWEAK) expression and skeletal muscle fiber-type transformation in these rats.Method:Fifty healthy male adult wistar rats were randomly divided into two groups:a normal control group(n=20) and a model group (n=30). The COPD rat model were established by intratracheal instillation of PPE(20u/100g.Bw)and being exposed to cigarette smoke for100days,30minutes per day. The control group was not exposed to smoke but was in intratracheal instilled of the same amount of Saline on the same day. In the100th days the lung tissue and quadriceps femoris muscle were got from the rats.One of quadriceps femoris muscle were made into paraffin sections,the other one were kept into-80℃refrigerator. At the same time we measured the weight of the body and the quadriceps femoris muscle of the two groups of the rats. HE staining was used to observe the changes in the structure of two groups of rat lung tissue, while Myosin-ATPase staining was used to observe the change of skeletal muscle fiber-type composition.Then TWEAK and PGC-la were measured at the protein level by Immunohistochemical method and Western blotting.Results:1.The wall of the airway and lung tissue of COPD model group rats were infiltrated with inflammatory cells.The diagnosis of COPD was measμred by the lung function of the rats and observation of lung tissue biopsy. 2.The body weight and the weight of quadriceps femoris muscle of the COPD model group rats were significantly lower than those of the control group (P<0.05, P<0.05)3.Compared to the control group, an decreased proportion of type~fibers was observed in quadriceps femoris muscle of the COPD model group, with a concomitant increased proportion of type Ⅱ fibers (P<0.05)4.The expression of TWEAK of the COPD model group was significantly increased compared with that of the control group(P<0.05),while the expression of PGC-la of the COPD model group was significantly decreased compared with that of the control group(P<0.05)5. The expression of TWEAK in the quadriceps femoris muscle was negative correlated with the ratio of type Ⅰ fibers by the Correlation Analysis.At the same time,the expression of TWEAK was positive correlated with the ratio of type Ⅱ fibers.6.The expression of PGC-la in the quadriceps femoris muscle was positive correlated with the ratio of type Ⅰ fibers by the Correlation Analysis.At the same time,the expression of PGC-1α in the quadriceps femoris muscle was negative correlated with the ratio of type Ⅱ fibers.7.The expression of TWEAK in the quadriceps femoris muscle was negative correlated with the expression of PGC-la.Conclusion:1. In COPD, the quadriceps femoris muscle is characterized by a marked decrease in Type Ⅰ fiber proportion and an increase in Type Ⅱ fiber proportion.2. The increment of the expression of TWEAK in skeletal muscle may be an important mechanism of skeletal muscle fiber-type transformation of the COPD model rats.3. In the COPD model rats,the activation of TWEAK may decreased the expression of PGC-1α, and then leading to the change of skeletal muscle fiber-type composition. This paper include28charts、9tables and58references.