What are the differences between statin and the shortage of cellular cholesterol content in the pathology of rhabdomyolysis ?

他汀类药物是HMGCR的抑制剂，HMGCR是胆固醇合成的限速酶。尽管他汀类药物是治疗高胆固醇血症的有效药物，但他汀类药物的副作用是横纹肌溶解。为了了解他汀类药物引起横纹肌溶解的发病机制，我们建立了骨骼肌特异性HMGCR基因敲除小鼠。这些小鼠表现出与横纹肌溶解相同的表型。我们发现，在这些小鼠的骨骼肌中，通过自噬去除不足的线粒体是不受调控的。接下来，我们将确定HMGCR基因敲除小鼠骨骼肌中线粒体功能和自噬功能障碍的机制。

Statin is an inhibitor for HMGCR, which is a rate-limiting enzyme for cholesterol synthesis. Although statin is an effective drug for hypercholesterolemia, statin develops rhabdomyolysis as a side effect. To understand the mechanism of the pathogenesis of rhabdomyolysis by statin, we generated the skeletal muscle-specific HMGCR knockout mice. These mice showed the same phenotypes as rhabdomyolysis. We found that the removal of the insufficient mitochondria by autophagy was dysregulated in skeletal muscle of these mice. Next, we will determine the mechanism that mitochondria function and autophagy are dysfunctioned in skeletal muscle of HMGCR knockout mice.