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| 龟板提取物抑制细胞衰老缓解SOP小鼠骨量丢失及海马退变 |
| Plastrum testudinis extract inhibits cell senescence and alleviates bone mass loss and hippocampal degeneration in SOP mice |
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| DOI：10.3969/j.issn.1006-7108.2024.03.002 |
| 中文关键词: 龟板提取物 细胞衰老 老年性骨质疏松 骨量丢失 海马组织退变 |
| 英文关键词:plastrum testudinis extract cell senescence senile osteoporosis loss of bone mass hippocampal degeneration |
| 基金项目:国家自然科学基金（82274542，82274615，82205137，82205230）；广东省自然科学基金(2021A1515011247) |
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| 中文摘要: |
| 目的 探讨龟板提取物（Plastrum testudinis extract，后简称PTE）通过抑制细胞衰老缓解SOP小鼠的骨量丢失及海马退变的作用。方法 动物实验：应用传统半乳糖皮下注射+去势法建立老年性骨质疏松症（senile osteoporosis，SOP）模型，将C57/BL6小鼠分为雌性或雄性的CON组、SOP组、SOP+PTE组；SOP+PTE组在造模过程中用PTE 0.5 g/mL灌胃干预4周，取材前1周进行行为学实验，后取大脑、L4椎体，检测骨和海马组织形态学；细胞实验：利用过氧叔丁醇（TBHP）诱导MC3T3/HT22细胞衰老，分别观察诱导后HT22半乳糖苷酶染色、衰老标志物和MC3T3成骨、衰老标志物的变化及PTE相应的治疗效果。结果 ①MicroCT提示雌雄小鼠中，与CON组相比，SOP组骨量丢失，SOP+PTE组骨量则得到了恢复；骨HE切片结果与MicroCT结果相符；海马组织切片提示，与CON组相比，SOP组海马出现退变，而SOP+PTE组退变则得到缓解。在新物体识别实验和时序实验中，与CON、SOP组相比，雄性SOP+PTE组记忆能力明显恢复；但雌雄小鼠旷场实验均无明显变化。②TBHP可诱导MC3T3衰老，降低成骨能力及增加衰老蛋白表达，而当加入PTE后，均能逆转TBHP导致的成骨能力降低与蛋白下降；TBHP亦可增加HT22半乳糖苷酶染色区域，增加衰老蛋白表达，而加入PTE后，上述变化均得到逆转。结论 PTE通过抑制前成骨细胞与海马神经元细胞的衰老，缓解SOP小鼠的骨量丢失和海马衰老退变。 |
| 英文摘要: |
| Objective To investigate the effect of plastrum testudinis extract (PTE) in alleviation of bone loss and hippocampal degeneration in senile osteoporosis (SOP) mice by inhibiting cellular senescence. Methods Animal experiments: the traditional galactose subcutaneous injection + denervation method was applied to establish a SOP model. C57/BL6 mice were divided into female or male CON group, SOP group, and SOP+PTE group. Mice in SOP+PTE group was intervened with PTE 0.5 g/ml by gavage for 4 weeks during the modelling process. Behavioural experiments were carried out 1 week before sampling. The brain and L4 vertebrae were collected to detect bone and hippocampal histomorphology. Cellular experiments: MC3T3/HT22 cell senescence was induced by using tert-butyl peroxyhydroxypropanol (TBHP). The changes in HT22 galactosidase staining, senescence markers, and MC3T3 osteogenesis, senescence markers and the corresponding therapeutic effect of PTE were observed respectively after the induction. Results ①Micro CT results suggested that in both male and female mice, bone mass was lost in the SOP group compared to that in the CON group, while bone mass was restored in the SOP+PTE group. The results of bone HE section were in line with those of micro CT. Results in hippocampal tissue section suggested that hippocampal degeneration was observed in the SOP group compared to that in the CON group, while the degeneration was alleviated in the SOP+PTE group. In the new object recognition experiment and temporal sequence experiment, the memory ability of the male SOP+PTE group was significantly restored compared to that in the CON and SOP groups. However, there was no significant change in the absent field experiment in both male and female mice. ②TBHP induced MC3T3 senescence, decreased osteogenic capacity, and increased senescent protein expression. When PTE was added, it reversed the decrease in osteogenic capacity and protein decline caused by TBHP. TBHP also increased the HT22 galactosidase staining region and increased senescent protein expression. When PTE was added, the above changes were reversed. Conclusion PTE alleviates bone loss and hippocampal senescence in SOP mice by inhibiting the senescence of preosteoblasts and hippocampal neuronal cells. |
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