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脂蛋白脂酶(lipoprotein lipase,LPL)是甘油三酯分解的限速酶,LPL基因缺失会引起高血脂症,虽然发病率低,但到目前为止,尚无有效治疗手段。该文构建了用于纠正LPL缺失基因型的逆转录病毒载体MSCV-hLPL,结果表明,MSCV-hLPL可以高效侵染体外培养的细胞系C2C12、HEK293和3T3-L1,并且都可以产生具有活性的脂蛋白脂酶。利用MSCV-hLPL侵染后的C2C12、HEK293和3T3-L1,分别注射到裸鼠皮下组织,发现C2C12和3T3-L1可以分泌脂蛋白脂酶到临近的肌肉组织中,显著提高LPL活性。以上工作证明,基因治疗载体可以纠正脂蛋白脂酶缺失的基因型,而脂肪细胞和肌肉细胞移植入裸鼠体内后,均可以作为生物反应器产生具有活性的LPL。这是该领域中的一次开拓性尝试,为脂蛋白脂酶缺失症治疗方法的开发打下了坚实的基础。
Lipoprotein lipase (LPL) is a rate-limiting enzyme in the decomposition of triglycerides. LPL gene deletion causes hyperlipidemia. Although the incidence is low, so far there is no effective treatment. The retroviral vector MSCV-hLPL was constructed to correct the LPL deletion genotype. The results showed that MSCV-hLPL could efficiently infect the cell lines C2C12, HEK293 and 3T3-L1 cultured in vitro, and all of them could produce active Lipoprotein lipase. The C2C12, 3T3-L1 and C2C12 cells infected with MSCV-hLPL were respectively injected into the subcutaneous tissue of nude mice. It was found that C2C12 and 3T3-L1 secreted lipoprotein lipase to adjacent muscle tissue and significantly increased LPL activity. The above work proved that the gene therapy vector can correct the lipoprotein lipase-deficient genotype, and the adipocytes and muscle cells can be transplanted into the nude mice to produce the active LPL as a bioreactor. This is a pioneering attempt in this area, laying a solid foundation for the development of the treatment of lipoprotein lipase deficiency.