目的研究心肌梗死(简称心梗)后大鼠心脏Sema 3A及其受体neuropilin-1(NP-1)和电生理的变化。方法50只大鼠随机分为心梗组(n=30)和假手术组(n=20)。用结扎左冠状动脉前降支的方法制备大鼠心梗模型。8周后,测定大鼠梗死周边区心室颤动(简...目的研究心肌梗死(简称心梗)后大鼠心脏Sema 3A及其受体neuropilin-1(NP-1)和电生理的变化。方法50只大鼠随机分为心梗组(n=30)和假手术组(n=20)。用结扎左冠状动脉前降支的方法制备大鼠心梗模型。8周后,测定大鼠梗死周边区心室颤动(简称室颤)阈值和有效不应期;应用蛋白质印迹法和逆转录聚合酶链反应技术检测梗死周边区Sema 3A及其受体的蛋白和mRNA的表达。结果心梗后8周,大鼠梗死周边区心肌室颤阈值降低(7.1±4.1 V vs 13.0±2.1 V,P<0.05),有效不应期延长(76±9 ms vs 61±8 ms,P<0.05)。大鼠心脏梗死周边区Sema 3A蛋白和mRNA的相对值都显著的降低。但是,Sema 3A的受体蛋白和mRNA的相对值都明显的升高。结论心梗后大鼠心脏梗死周边区发生电重构;梗死周边区Sema 3A明显减少,Sema 3A的受体明显增加。展开更多
Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bo...Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.展开更多
文摘目的研究心肌梗死(简称心梗)后大鼠心脏Sema 3A及其受体neuropilin-1(NP-1)和电生理的变化。方法50只大鼠随机分为心梗组(n=30)和假手术组(n=20)。用结扎左冠状动脉前降支的方法制备大鼠心梗模型。8周后,测定大鼠梗死周边区心室颤动(简称室颤)阈值和有效不应期;应用蛋白质印迹法和逆转录聚合酶链反应技术检测梗死周边区Sema 3A及其受体的蛋白和mRNA的表达。结果心梗后8周,大鼠梗死周边区心肌室颤阈值降低(7.1±4.1 V vs 13.0±2.1 V,P<0.05),有效不应期延长(76±9 ms vs 61±8 ms,P<0.05)。大鼠心脏梗死周边区Sema 3A蛋白和mRNA的相对值都显著的降低。但是,Sema 3A的受体蛋白和mRNA的相对值都明显的升高。结论心梗后大鼠心脏梗死周边区发生电重构;梗死周边区Sema 3A明显减少,Sema 3A的受体明显增加。
基金supported in part by National Natural Science Foundation of China(32271364 & 31971240)Interdisciplinary innovation project from West China Hospital of Stomatology, Sichuan University(RD-03-202305)。
文摘Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
