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鹼性結締組織生長因子(bFGF)是一種分子量在16至25kDa,具多種生物活性的聚多胜月太,文獻上記載,在各種不同的腦損傷模型之受傷區域附近,發現有bFGF蛋白質或訊息核醣核酸量的增加,若事先並外在給予受傷神經細胞鹼性結締組織生長因子,則發現其可減低組織傷害程度。先前,本實驗室於局部腦缺血的動物模型中,利用北方轉漬法與原位雜交技術,發現在腦缺血迴流刺激下,鹼性結締組織生長因子的訊息核醣核酸會隨著位置和時間的不同而有不同的變化。然而,此模型乃利用外來人工方式,以造成特定區域的缺血,在模擬人類的中風過程中有其限制性,故本論文改以SHR-SP為動物模型,並以北方轉漬法及免疫組織化學染色法偵測、觀察鹼性結締組織生長因子的訊息核醣核酸和蛋白質表現,是否與SHR-SP之中風發展及中風傷害區域有相關性。實驗結果顯示,本論文所觀察到的鹼性結締組織生長因子之訊息核醣核酸的種類(species),以6.0Kb為主,其於中樞神經系統之分佈,以海馬迴含量最高,其餘依次為大腦皮質、下大腦皮質,而小腦的表現量最少。比較WKY,SHR與SHR-SP三品種老鼠的鹼性結締組織生長因子之訊息核醣核酸含量,發現只有在大腦皮質才有顯著的不同,其它區域則無明顯差異,且此差異會隨SHR-SP年齡的增長而逐漸加大,於其生命的晚期(約38週)時,達到最高點,而其總訊息核醣核酸含量則有隨年齡之增長而下降的趨勢。免疫組織染色法的結果,進一步支持北方轉漬法的結論,即鹼性結締組織生長因子之蛋白質表現量在SHR-SP之大腦皮質部位較WKY及SHR高,且主要分佈在大腦皮質的額、枕葉區域,蘇木紫與伊紅染色法更進一步支持這些區域為腦創傷區。總之,本研究結果清楚的頭示,鹼性結締組織生長因子於SHR-SP之中風發展及迴流刺激過程中,可能在中樞神經系統組織修補、功能恢復及增加神經可塑性中扮演相當重要角色。 Basic fibroblast growth factor(bFGF) is a biologically active polypeptide with mitogenic, angiogenic and neurotrophic properties. Significant increase in the level of bFGF immunoreactivity were found after neuronal injury. In the present study, we examine the temporal and spatial expression of bFGF mRNA and protein during ischemia- reperfusion, using a recent developed rat strain: spontaneously hypertensive rats-stroke prone (SHR-SP). The advantage for using this model are no invasive surgical operation is needed, eliminate the complication of mechanical injury, intracranal pressure, autoregulation and anesthetic effect. Data indicated that in the cortex of 4-week-old rats have higher amount of total RNA compare to 12-, 26- and 38-week-old rats. The regional distribution study indicated that among all the strains and different ages of rats, hippocampus contained the highest level of bFGF mRNA followed by cortex and subcortex; cerebellum has the least amount. Significant difference in the amount of bFGF mRNA were found only in the cortical area of 26 and 38-week-old SHR-SP, at the latter stage of life span, which showed an one fold increase in the mRNA quantity. This increase is in line with the literature reported that the most vulnerable region of SHR-SP is the cortical area (69.8% of incidence ). Similar increase in the amount of bFGF immunoreactivity also been found in the anteromedial and occipital area of left cortical hemisphere. Injured cortical area and the surrounding area showed a higher amount of expression than the corresponding region of WKY and SHR, especially in the surrounding area. H&E staining further support this finding. In summary, our results indicated an important role of bFGF during stroke induced neuronal injury and/or recovery.
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