p110δ突变失活上调血管MMPs表达并引发血管壁结构损伤

Improved MMPs in p110δ-mutant mice contributes to rupture of thoracic aorta

目的：研究p110δD910A基因突变失活（p110δ-mutant）对动脉血管结构的影响及机制。方法：选取8周龄雄性的野生型（WT）小鼠与p110δ-mutant小鼠（n=20;20-25 g）,取胸主动脉进行石蜡包埋,HE染色,采用免疫组化、免疫荧光以及real-time PCR等方法,研究p110δ突变对小鼠动脉血管形态变化的影响及机制。结果：与WT相比,p110δ突变失活后小鼠主动脉血管壁变薄,管腔变大。p110δ突变失活后主动脉血管壁形态紊乱,弹力纤维局部断裂,血管中内皮细胞凋亡。p110δ突变失活后主动脉血管α平滑肌肌动蛋白（α-SMA）表达量、胶原Ⅰ和胶原Ⅳ含量减少。p110δ突变失活后主动脉血管中的基质金属蛋白酶-3（MMP-3）和MMP-9的mRNA水平明显升高。结论：PI3K活性在维持小鼠动脉血管的正常形态中起重要作用,p110δ突变失活后可能通过上调基质金属蛋白酶的表达促进血管壁结构的破坏。

AIM： To observe the pathological characteristics of the thoracic aorta in the p110δ-mutant mice.METHODS： The thoracic aorta of wild type male mice and p110δ-deficient male mice（ 8 weeks old） were achieved. HE,IHC and IF staining were performed on the paraffin fixed arterial sections. The mRNA expression was detected by real-time PCR. RESULTS： The vascular wall became thinner and the vessel diameter enlarged after inactivating mutation of p110δ.After inactivating mutation of p110δ,the smooth muscle cells showed vacuolar degeneration,morphological disorders and elastic fiber local fracture. The collagen content was reduced after inactivating mutation of p110δ. The expression of matrix metalloproteinase-3（ MMP-3） and MMP-9 was up-regulated after inactivating mutation of p110δ. CONCLUSION： Inactivating mutation of p110δ may contribute to the injury of artery vascular wall by up-regulation of MMPs.