| Chronic alcoholic myopathy is a kind of myopathy because of long time alcohol misuse. It has been reported that there are about 40%-60%alcoholist whose muscle was affected. Their frequently clinical appearances were having difficulties in gait, various muscle symptoms such as cramps, local pain and reduced muscle mass. So, chronic alcoholic myopathy affects the quality of patients'life severely. However, there are merely few clinical and experimental reports about CAM in our country, even fewer than alcoholic liver disease (ALD) and alcoholic myocardiopathy. Lots of researchers have observed that tissue inhibitor of metalloproteinases-1,2(TIMP-1,2)play a key role in skeletal muscle weakness,amyotrophy and extracellular matrix (ECM) fibrosis. We experimentalize in order to investigate these factors whether express in alcoholic myopathy or not. By doing this, we may find some available method and it is important for the prevention and therapy of chronic alcohol myopathy.Objectives: The project is on the basis of chronic alcoholic myopathy model of rat, to observe the expression of TIMP-1,2 in muscle cell, observe the possible function in the mechanism of alcohol myopathy, move forward a single step to explain the pathogenesy of this disease from gene and protein level. We do this in order to provide rationale for clinical prevention and cure in chronic alcoholic myopathy. We also provide a helpful platform for other metabolic myopathy.Methods: (1) 60 healthy, male, Sprague-Dawley rats were chosen to sep up the CAM rat myopathy model, to observe the rat body weight, the change of praxiology and the patho-change of muscle tissue. (2) Operated group was treated with alcohol. Control group was given NS which contain the same volume to ethanol. At the same time, they are feeding the same improved food with high fats and sufficient nutrients. At the end of 12 weeks, rats were killed, taken the muscle of posterior limb, after separating the gastroenemius, soleus and plantaris, to prepare the frozen section of the each kind of muscle respectively to be confirmed to form the myopathy model by the histochemical stain. (3) RT-PCR and Western blot were respectively used to detect the expression of TIMP-1 and TIMP-2.Results:(1) After being given alcohol, the pathological lesion of theâ…¡-type fibers is more severe than theâ… -type fibers, the treated rat show up the typical patho-change, such as the myofibrosis, necrosis, the shapes of the muscle fiber atrophy become triangle, strip or irregular and muscle fiber regenerate, the connective tissue among the muscle tissue become hyperplasia, and so on.(2) RT-PCR method shows that with the alcohol taking, the expression of TIMP-1 increase gradually, especially in gastroenemius. The expression of TIMPP-2 has no significant difference between operated group and normal controls.(3) Western blot method shows that the expression of TIMP-1 increase gradually on protein level. Ethanol can activate and promote the expression of TIMP-1. As the same with the result of RT-PCR, TIMP-2 increases quietly.Conclusions:(1) The up-regulation of the expression of TIMP-1 perhaps takes part in the accrementition and reconstitution of mesenchymal fibers (â… -type collagen dominates in mesenchymal, ratio ofâ… /â…¢increases). TIMP-1 can facilitate inflammatory cell infiltration, aggravate the development of CAM.(2) TIMP-2 potentially does not take part in the accrementition and reconstitution of mesenchymal fibers directly. |
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