Angelica And Chuanxiong Tail-suspended Rat Soleus Muscle And Its Mechanism

BackgroundA great deal of scientific data and experiments have indicated weightlessness andsimulated microgravity can lead to apparent muscle atrophy. Muscle atrophy affects astronaut performance both in- and post flight. Therefore, it is important to find effective drugs to prevent or treat muscle atrophy caused by weightlessness in the fields of clinical, aerospace and rehabilitation medicine. Under weightlessness or stimulated weightlessness conditions, postural muscle spindle afferent discharge declines, which may contribute to the develop of muscle atrophy. Countermeasures, which can excite muscle spindles such as intermittent stretch, have been shown to alleviate disuse atrophy. On the other hand, real or simulated microgravity may evoke cardiac and hemostatic problems, several reports have documented the risk of deep venous thrombosis or capillary thromboembolism increased. Accordingly, inactivity-induced thrombosis may form a vicious cycle in combination with muscle atrophy. Therefore, drugs that enhance the afferent muscle spindle discharge and at the same time improve muscular perfusion would therefore be ideal to fight weightlessness induced muscle atrophy. Therefore, we choose Angelica sinensis that activate the blood circulation, which can distinctively tingle the spontaneous electrical activity of muscle spindle. Another classical TCM we are interested in is Ligusticum whose main effective ingredient to activate blood circulation is Ligustrazine. Ligustrazine may also be useful to fight weightlessness induced muscle atrophy. If the Ligustrazine is the main component in Ligusticum to fight weightlessness induced muscle atrophy? We will investigate the question in this study. The tail-suspended rat was taken as model to research the morphological structure, biochemical metabolism, hemorrheology of skeletal muscle, so as to provide experimental data for drug development of muscle atrophy. Objective: This research attempts to observe the effects of Angelica sinensis and Ligusticum on muscle atrophy caused by microgravity and probes into their mechanism. Investigate if the Ligustrazine is the main component in Ligusticum to fight weightlessness induced muscle atrophy?Methods: Tail-suspended rat was taken as the disuse atrophy model. (1) The ratwas treated with Angelica sinensis and Ligusticum. The effects of Angelica sinensis and Ligusticum on the structure and CSA of soleus muscle in tail-suspended rat were studied and compared respectively. (2) Immunohistochemical method was used to study the effects of expression of MHC on Angelica sinensis and Ligusticum in tail-suspended rat soleus muscle. (3) We observed the effect of Angelica sinensis and Ligusticum on hemorrheology by whole blood viscocity, blood plasm viscocity, , hematocrit value and erythrocyte deformability. (4) The effects of Angelica sinensis and Ligusticum on the ultrastructure of soleus muscle spindle in tail-suspended rat were studied and compared respectively, by electron microscope.Results:(1) Effects of Angelica sinensis and Ligusticum on the structure and CSA ofsoleus muscle in tail-suspended rat1)Compared to TS+W group, muscle fiber of treatment was compacter, deteriorated shape was improved。2) Angelica sinensis could effectively prevent the decreasing of CSA caused by microgravity. 25% type I fiber CSA increase in TS+Lig above TS+W just failed to reach the generally accepted level of statistical significance. Compared to data from our previous work, it is obvious that the atrophy- alleviating effect of a similar dose of Ligusticum is weaker than that of Ligustrazine. Accordingly, we surmise that Ligustrazine is the main ingredient in Ligusticum to alleviate muscle atrophy in simulated weightlessness.(2) Effects of Angelica sinensis and Ligusticum on tail-suspended rat soleus muscle expression of MHC and fiber percentage1) After 14 days hindlimb-unloading plus intragastric water instillation (TS+W), the expression of fast muscle MHC increased, slow muscle MHC reduced. Treated with Angelica sinensis and Ligusticum, the expression of fast muscle MHC reduced, and slow muscle MHC increased. 2) Compared to TS+W, type I muscle of treated increased significantly, and type II muscle decreased.(3) Effects of Angelica sinensis and Ligusticum on hemorrheology of tail-suspended ratAfter 14d tail-suspension, the whole blood viscocity, blood plasm viscocity, and erythrocyte deformability of rat increased significantly and hematocrit value reduces. After treatment with Angelica sinensis and Ligusticum for 14 days, the change of them was obviously under control. The results showed that one of the mechanisms of anti- muscle atrophy of Angelica sinensis and Ligusticum was possibly realized by improving the red blood cell mass and promoting blood circulation.(4) Effects of Angelica sinensis and Ligusticum on the ultrastructure of soleusmuscle spindle in tail-suspended ratCompared to TS+W group, ultrastructure of soleus muscle spindle was compacter, deteriorated shape was improved。Another mechanisms of anti- muscle atrophy of Angelica sinensis and Ligusticum was possibly realized by exciting muscle spindles.Conclusion:(1) Angelica sinensis and Ligusticum could prevent the change of microstructure in muscle fibres caused by simulated weightlessness, and Angelica sinensis could prevent the decrease of CSA. The effect of Ligusticum is weaker than Ligustrazine, so Ligustrazine is the main ingredient to alleviate muscle atrophy in simulated weightlessness in Ligusticum.(2) Angelica sinensis and Ligusticum could prevent the increase of MHC-II caused by simulated weightlessness.(3) Angelica sinensis and Ligusticum could drastically inhibit the change ofhemorrheology caused by simulated weightlessness.(4) Angelica sinensis and Ligusticum could prevent the changes ofultrastructure in muscle fibres caused by simulated weightlessness.