【摘要】 目的：探讨人参皂苷Rg1调节miR-144-3p对实验性脑出血大鼠神经炎症和血脑屏障损伤的影响，以及对甲酰基肽受体2(FPR2)/p38通路的调控作用。方法：90只SD大鼠随机分为对照组、脑出血组、人参皂苷Rg1低剂量组（10 mg/kg）、人参皂苷Rg1高剂量组（40 mg/kg）、人参皂苷Rg1高剂量+ago-miR-144-3p组（40 mg/kg人参皂苷Rg1+ago-miR-144-3p），每组18只，除对照组外均通过右侧尾状核注射胶原酶Ⅱ法构建实验性脑出血大鼠模型，按照各组要求腹腔注射给药以及脑内注射给药。对大鼠神经功能损伤进行评分；干湿比重法测定大鼠脑含水量；ELISA检测大鼠脑组织匀浆TNF-α、IL-6、IL-1β水平；电镜观察脑水肿周围超微结构；伊文思蓝（EB）法测定大鼠血脑屏障通透性；qRT-PCR与Western blot测定miR-144-3p/FPR2/p38通路表达。结果：与对照组相比，脑出血组大鼠血脑屏障损伤加重，大鼠神经功能损伤评分、脑含水量、脑组织匀浆miR-144-3p、TNF-α、IL-6、IL-1β、p38 mRNA、p-p38/p38表达增加（P<0.05）,FPR2 mRNA与蛋白表达降低（P<0.05）；与脑出血组相比，人参皂苷Rg1低剂量组、人参皂苷Rg1高剂量组大鼠血脑屏障损伤减轻，神经功能损伤评分、脑含水量、脑组织匀浆miR-144-3p、TNF-α、IL-6、IL-1β、p38 mRNA、p-p38/p38表达降低（P<0.05）,FPR2 mRNA与蛋白表达升高（P<0.05）;ago-miR-144-3p可逆转人参皂苷Rg1对大鼠血脑屏障、神经炎症的保护作用（P<0.05）。结论：人参皂苷Rg1可能通过调控miR-144-3p/FPR2/p38轴抑制大鼠血脑屏障损伤及神经炎症。更多还原

【Abstract】 Objective:To investigate influences of ginsenoside Rg1 regulating miR-144-3p on neuroinflammation and bloodbrain barrier damage in rats with experimental cerebral hemorrhage, and its regulation on formyl peptide receptor 2(FPR2)/p38 pathway. Methods:Ninety SD rats were randomly divided into control group, cerebral hemorrhage group, ginsenoside Rg1 low-dose group(10 mg/kg), ginsenoside Rg1 high-dose group(40 mg/kg), ginsenoside Rg1 high-dose+ago-miR-144-3p group(40 mg/kg ginsenoside Rg1+ago-miR-144-3p), with 18 mice in each group. Except for control group, experimental intracerebral hemorrhage rat model was constructed by injecting collagenase Ⅱ into right caudate nucleus, and then each group was given intraperitoneal administration and intracerebral injection as required. Neurological damage in rats was scored; rat brain water content was determined by dry-wet specific gravity method; levels of TNF-α, IL-6 and IL-1β in rat brain tissues homogenate were determined by ELISA; ultrastructure around cerebral edema was observed by electron microscope; permeability of blood-brain barrier in rats was determined by Evans blue(EB) method; expressions of miR-144-3p/FPR2/p38 pathway were determined by qRT-PCR and Western blot. Results:Compared with control group, blood-brain barrier damage was aggravated in cerebral hemorrhage group, neurological function damage score, brain water content, miR-144-3p, TNF-α, IL-6, IL-1β, p38 mRNA, p-p38/p38 expressions in brain homogenate were increased(P<0.05), FPR2 mRNA and protein expressions were decreased(P<0.05); compared with cerebral hemorrhage group, blood-brain barrier damage was reduced in ginsenoside Rg1 low-dose group and ginsenoside Rg1 high-dose group, neurological function damage score, brain water content, miR-144-3p, TNF-α, IL-6, IL-1β, p38 mRNA, p-p38/p38 expressions in brain homogenate were decreased(P<0.05), FPR2 mRNA and protein expressions were increased(P<0.05); ago-miR-144-3p was able to reverse protective effects of ginsenoside Rg1 on blood-brain barrier and neuroinflammation in rats(P<0.05). Conclusion:Ginsenoside Rg1 may inhibit blood-brain barrier damage and neuroinflammation in rats by regulating miR-144-3p/FPR2/p38 axis.更多还原