缺氧在烧伤后早期心肌损害中起着重要的作用。自噬是细胞依赖溶酶体的分解代谢过程，在心肌缺血缺氧性损害中发挥重要作用，但其调节机制还不清楚。我们以往研究发现缺氧可激活p38激酶引起MAP4磷酸化，导致心肌细胞微管解聚。而文献报道微管解聚可抑制自噬。我们前期研究发现缺氧时心肌细胞自噬活性下降，推测微管解聚可能是缺氧抑制心肌细胞自噬的重要机制。申报者提出 “p38/MAPK激活介导的MAP4磷酸化导致微管解聚是缺氧心肌细胞自噬活性下降的关键分子机制”的科学假设。本研究拟观察缺氧时心肌细胞自噬的变化；构建MAP4磷酸化位点突变腺病毒载体，研究缺氧后MAP4 磷酸化改变及其在自噬调节中的作用和机制。通过研究，旨在证明MAP4 是一种自噬调节蛋白，磷酸化是其调节缺氧心肌细胞自噬的重要机制，并初步阐明p38/MAPK是其上游激酶通路。为临床上减轻缺氧心肌损害提供新的靶点和实验依据。

Hypoxia plays an important role in the early myocardial damage induced by burns. Autophagy is a cellular lysosomal catabolism process, which plays an important role in myocardial ischemia and hypoxia damage, but the mechanism is unclear. Our early study found that hypoxia can activate p38 kinase induced MAP4 phosphorylation, leading to microtubule depolymerization. While the literature reports that microtubule depolymerization can lead to inhibition of autophagy. Our previous study found that myocardial autophagy was inhibited in hypoxic conditions. We speculated that microtubule depolymerization may be an important mechanism for cardiomyocyte autophagy affected by hypoxia. We hypothesise that MAP4 is a key autophagy regulation protein, and the p38/MAPK activation and followed MAP4 phosphorylation induced by hypoxia lead to microtubule depolymerization and inhibition of autophagy. This study intends to observe the changes of cardiomyocyte autophagy during hypoxia, and constructing MAP4 phosphorylation site mutation adenovirus vector. In order to make clear the functions and mechanisms of MAP4 phosphorylation on the cardiomyocyte autophagy in hypoxic conditions. This work aims to prove that activation of p38/MAPK mediated MAP4 phosphorylation results in depolymerization of microtubules is a key molecular mechanism of hypoxic cardiomyocytes decreased autophagic activity. The project is expected to provide new targets and experimental basis for alleviating myocardial ischemia and hypoxia damage.