Effect of atractylenolide Ⅲ on stroke in spontaneously hypertensive rats and its mechanism
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摘要:目的
探讨白术内酯Ⅲ（A Ⅲ）通过微小RNA-296-5p（miR-296-5p）对自发性高血压大鼠（SHR）脑卒中的作用及可能机制。
方法使SHR连续2个月自由饮用0.9%氯化钠溶液，然后给予1%氯化钠溶液喂养，构建SHR脑卒中模型。将模型大鼠分为模型组（Model组）、A Ⅲ低剂量组（A Ⅲ-L组）、A Ⅲ高剂量组（A Ⅲ-H组）、阳性药物尼莫地平组（Nim组）、miR-296-5p激动剂组（miR-296-5p agomir组）、agomir NC组、A Ⅲ-H+miR-296-5p agomir组、A Ⅲ-H+agomir NC组，每组12只。检测并记录大鼠神经症状评分、平均动脉压、存活时间、血小板黏附率变化，采用苏木素-伊红（HE）染色法检测大鼠脑组织海马CA1区病理变化，采用实时荧光定量聚合酶链反应（qRT-PCR）检测海马CA1区中miR-296-5p表达。
结果与NC组比较，Model组大鼠神经症状评分、平均动脉压、血小板黏附率、miR-296-5p表达升高，存活时间缩短，海马CA1区病理损伤严重，差异有统计学意义（P < 0.05）；与Model组比较，A Ⅲ-L组、A Ⅲ-H组、Nim组大鼠神经症状评分、平均动脉压、血小板黏附率、miR-296-5p表达降低，存活时间延长，海马CA1区病理损伤减轻，差异有统计学意义（P < 0.05）；与Model组、agomir NC组比较，miR-296-5p agomir组大鼠神经症状评分、平均动脉压、血小板黏附率、miR-296-5p表达升高，存活时间缩短，海马CA1区病理损伤加剧，差异有统计学意义（P < 0.05）；与A Ⅲ-H组、A Ⅲ-H+agomir NC组比较，A Ⅲ-H+miR-296-5p agomir组大鼠神经症状评分、平均动脉压、血小板黏附率、miR-296-5p表达升高，存活时间缩短，海马CA1区病理损伤严重，差异有统计学意义（P < 0.05）。
结论A Ⅲ可能通过抑制miR-296-5p表达对SHR脑卒中起到治疗作用。
Abstract:ObjectiveTo investigate the effect of atractylenolide Ⅲ (A Ⅲ) on stroke in spontaneously hypertensive rats by regulating microRNA-296-5p(miR-296-5p)expression.
MethodsThe spontaneously hypertensive rats (SHR) were given 0.9% sodium chloride solution freely for 2 months, and then fed with 1% sodium chloride solution to establish the stroke model of SHR. The rat models were randomly grouped into Model group, A Ⅲ low-dose group (A Ⅲ-L group), A Ⅲ high-dose group (A Ⅲ-H group), positive drug nimodipine group (Nim group), miR-296-5p agonist group(miR-296-5p agomir group), agomir NC group, A Ⅲ-H+miR-296-5p agomir group, and A Ⅲ-H+agomir NC group, with 12 in each group. The changes in neurological symptom scores, average arterial pressure, survival time, and platelet adhesion rate were detected and recorded; hematoxylin and eosin (HE) staining was applied to detect pathological changes in the CA1 region of the rat hippocampus; quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to detect the expression of miR-296-5p in the hippocampal CA1 region.
ResultsCompared with the NC group, the Model group showed increases in neurological symptom score, mean arterial pressure, platelet adhesion rate, miR-296-5p expression, shortened survival time, and severe pathological damage to the hippocampal CA1 area (P < 0.05); compared with the Model group, the neurological symptom scores, mean arterial pressure, platelet adhesion rate, and miR-296-5p expression in the A Ⅲ-L, A Ⅲ-H, and Nim groups decreased, the survival time was prolonged, and the pathological damage in the CA1 area of the hippocampus was alleviated(P < 0.05); compared with Model group and agomir NC group, neurological symptom score, mean arterial pressure, platelet adhesion rate and miR-296-5p expression of rats in the miR-296-5p agomir group were increased, survival time was shortened, and pathological damage in hippocampal CA1 region was aggravated (P < 0.05). compared with the A Ⅲ-H group and the AⅢ-H+agomir NC group, the neurological symptom score, average arterial pressure, platelet adhesion rate and miR-296-5p expression of rats were increased, the survival time was shortened, and the pathological damage in hippocampal CA1 region was serious in the AIII-H+miR-296-5p agomir group (P < 0.05).
ConclusionA Ⅲ may treat SHR stroke by inhibiting the expression of miR-296-5p.
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Keywords:
- atractylenolide Ⅲ /
- spontaneous hypertension /
- stroke /
- microRNA-296-5p /
- neurological symptoms /
- platelet adhesion
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表 1 各组大鼠神经症状评分和平均动脉压比较(x±s)
组别 n 神经症状评分/分 平均动脉压/kPa NC组 12 0 11.06±0.24 Model组 12 2.94±0.11* 17.75±0.26* A Ⅲ-L组 12 2.51±0.08# 15.58±0.18# A Ⅲ-H组 12 1.25±0.06#▽ 12.29±0.14#▽ Nim组 12 1.23±0.07#▽ 12.28±0.13#▽ agomir NC组 12 2.95±0.12 17.77±0.24 miR-296-5p agomir组 12 3.63±0.12#△ 19.95±0.20#△ A Ⅲ-H+agomir NC组 12 1.24±0.08 12.30±0.15 A Ⅲ-H+miR-296-5p agomir组 12 2.45±0.09▼▲ 14.92±0.13▼▲ 与NC组比较, * P < 0.05; 与Model组比较, #P < 0.05; 与A Ⅲ-L组比较, ▽P < 0.05; 与A Ⅲ-H组比较, ▼P < 0.05; 与agomir NC组比较, △P < 0.05; 与A Ⅲ-H+agomir NC组比较, ▲P < 0.05。 
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表 2 各组大鼠存活时间和血小板黏附率比较(x±s)
组别 n 存活时间/d 血小板黏附率/% NC组 12 42.00 26.62±1.35 Model组 12 26.72±1.38* 45.85±1.86* A Ⅲ-L组 12 31.14±1.86# 40.27±1.78# A Ⅲ-H组 12 38.23±1.07#▽ 33.52±1.65#▽ Nim组 12 38.21±1.05#▽ 33.46±1.59#▽ agomir NC组 12 26.78±1.41 45.76±1.83 miR-296-5p agomir组 12 19.44±0.66#△ 49.17±1.82#△ A Ⅲ-H+agomir NC组 12 37.96±1.04 32.98±1.45 A Ⅲ-H+miR-296-5p agomir组 12 30.55±1.45▼▲ 38.83±1.76▼▲ 与NC组比较, * P < 0.05; 与Model组比较, #P < 0.05; 与A Ⅲ-L组比较, ▽P < 0.05; 与A Ⅲ-H组比较, ▼P < 0.05; 与agomir NC组比较, △P < 0.05; 与A Ⅲ-H+agomir NC组比较, ▲P < 0.05。
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表 3 各组大鼠脑组织海马CA1区miR-296-5p表达比较(x±s)
组别 n miR-296-5p NC组 6 1.00 Model组 6 2.86±0.13* A Ⅲ-L组 6 2.15±0.14# A Ⅲ-H组 6 1.43±0.12#▽ Nim组 6 1.44±0.13#▽ agomir NC组 6 2.89±0.14 miR-296-5p agomir组 6 4.75±0.34#△ A Ⅲ-H+agomir NC组 6 1.46±0.15 A Ⅲ-H+miR-296-5p agomir组 6 2.15±0.16▼▲ 与NC组比较, * P < 0.05; 与Model组比较, #P < 0.05;
与A Ⅲ-L组比较, ▽P < 0.05; 与A Ⅲ-H组比较, ▼P < 0.05;
与agomir NC组比较, △P < 0.05;
与A Ⅲ-H+agomir NC组比较，▲P < 0.05。
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