甲狀腺激素對(duì)大鼠腦缺血再灌注損傷后NF-κB與TNF-α表達(dá)的影響
發(fā)布時(shí)間：2018-11-17 06:39
【摘要】：研究背景缺血性腦血管病是一種發(fā)病率高、致殘率高、死亡率高的三高疾病,嚴(yán)重威脅著人類的健康并影響著生活質(zhì)量。近年來(lái)關(guān)于缺血性腦血管病的治療主要有動(dòng)靜脈溶栓、機(jī)械取栓等,主要目的是為了及時(shí)再通血流,挽救缺血半暗帶。血管再通后雖使組織細(xì)胞重新獲得了新鮮的血流,避免了進(jìn)一步的缺血缺氧,但隨之而帶來(lái)的缺血再灌注損傷問(wèn)題也是目前最突出且研究熱門的問(wèn)題。缺血再灌注損傷是指當(dāng)組織重新獲得血流后,組織器官不僅沒(méi)有得到好轉(zhuǎn),反而出現(xiàn)新的損傷。缺血再灌注損傷涉及了多種復(fù)雜的病理過(guò)程,炎癥反應(yīng)是參與其中重要的病理機(jī)制之一,其最終作用結(jié)果可導(dǎo)致神經(jīng)元損傷死亡。炎性因子核轉(zhuǎn)錄因子(nuclear factor-kappa B,NF-κB)、腫瘤壞死因子(tumor necrosis factor,TNF-α)在腦缺血后容易表達(dá),以此做為觀察指標(biāo),可以較好的模擬人體內(nèi)腦缺血的病理生理過(guò)程。我們知道,甲狀腺激素對(duì)中樞神經(jīng)系統(tǒng)的發(fā)育具有不可忽視的影響。但目前關(guān)于甲狀腺激素對(duì)缺血再灌注損傷(Ischemic-reperfusion,IR)作用的報(bào)道相對(duì)較少。本實(shí)驗(yàn)通過(guò)制作大鼠大腦中動(dòng)脈閉塞(middle cerebral artery occlusion,MCAO)模型,觀察了甲狀腺激素(Triiodothyronine,T3)對(duì)缺血再灌注后炎性因子NF-κB、TNF-α表達(dá)的影響,探討了甲狀腺激素在炎癥反應(yīng)通路中的作用,為腦血管病的治療提供了新思路。研究目的探討甲狀腺激素(T3)對(duì)大鼠腦缺血再灌注損傷(IR)后缺血側(cè)皮質(zhì)NF-κB、TNF-α表達(dá)的影響。研究方法將96只健康成年SD雄性大鼠隨機(jī)分為假手術(shù)組、假手術(shù)+T3組、IR組、IR+T3組,采用改良線栓法制作大鼠大腦中動(dòng)脈缺血2h再灌注模型,假手術(shù)+T3組及IR+T3組在造模后1h再灌注后6h分別腹腔注射甲狀腺激素l0 ug/100 g,其余兩組分別腹腔注射等量生理鹽水。在大鼠麻醉蘇醒后24h,根據(jù)Longa5分制法對(duì)其進(jìn)行神經(jīng)功能評(píng)分,于再灌注24h后取腦組織。用2,3,5-氯化三苯基四氮唑(2,3,5-Triphenyltetrazolium chloride,TTC)染色法檢測(cè)大鼠腦梗死灶的面積百分比,HE染色法觀察腦組織的病理結(jié)構(gòu)的改變。采用實(shí)時(shí)熒光定量PCR(Real-Time PCR)法檢測(cè)大鼠缺血側(cè)皮質(zhì)NF-κB mRNA、TNF-αmRNA的表達(dá)水平,免疫組化染色法檢測(cè)缺血側(cè)皮質(zhì)NF-κB、TNF-α蛋白表達(dá)變化。結(jié)果1.IR+T3組大鼠的神經(jīng)功能評(píng)分及腦梗死灶面積百分比較IR組的明顯降低(P0.05)。2.HE染色結(jié)果顯示IR+T3組大鼠腦組織病理?yè)p傷較IR組明顯減輕。3.Real-time PCR及免疫組織化學(xué)結(jié)果顯示,假手術(shù)組、假手術(shù)+T3組大鼠缺血側(cè)皮質(zhì)NF-κB mRNA、TNF-αmRNA及其蛋白表達(dá)量無(wú)明顯差異。與假手術(shù)組相比,IR組大鼠缺血側(cè)皮質(zhì)NF-κB mRNA、TNF-αmRNA及其蛋白表達(dá)量顯著增多(P0.05);與IR組相比,IR+T3組大鼠NF-κB mRNA、TNF-αmRNA及其蛋白表達(dá)量顯著減少(P0.05)。結(jié)論1.甲狀腺激素對(duì)大鼠腦缺血再灌注損傷具有保護(hù)作用。2.甲狀腺激素的保護(hù)作用是通過(guò)下調(diào)炎性因子NF-κB、TNF-α的表達(dá)來(lái)實(shí)現(xiàn)的。
[Abstract]:Background Ischemic cerebrovascular disease (ICVD) is a kind of three high diseases with high morbidity, high disability rate and high mortality rate. It is a serious threat to human health and affects the quality of life. In recent years, the treatment of ischemic cerebrovascular disease mainly includes arteriovenous thrombolysis, mechanical thrombolysis and so on. The main purpose is to recanalize the blood flow and save the ischemic penumbra in time. Although the tissue cells can get fresh blood flow again and avoid further ischemia and hypoxia after vascular recanalization, the problem of ischemia reperfusion injury is also the most prominent and hot issue at present. Ischemia-reperfusion injury refers to the new injury of tissue and organ after the tissue regains blood flow. Ischemia-reperfusion injury involves a variety of complex pathological processes, inflammatory response is one of the important pathological mechanisms involved, and the final result can lead to the death of neurons. The expression of nuclear factor-kappa BNF- 魏 B), tumor necrosis factor (tumor necrosis factor,TNF- 偽) is easy after cerebral ischemia, which can be used as an index to simulate the pathophysiological process of cerebral ischemia in human body. Thyroid hormones are known to have an important effect on the development of the central nervous system. However, there are few reports about the effect of thyroid hormone on ischemia reperfusion injury (Ischemic-reperfusion,IR). The effect of thyroid hormone (Triiodothyronine,T3) on the expression of inflammatory factor NF- 魏 B (TNF- 偽) in rats with middle cerebral artery occlusion (MCAO) was studied. To explore the role of thyroid hormone in inflammatory response pathway and provide a new idea for the treatment of cerebrovascular disease. Objective to investigate the effect of thyroid hormone (T 3) on the expression of NF- 魏 B tNF- 偽 in ischemic cortex of rats after cerebral ischemia reperfusion injury (IR). Methods 96 healthy adult SD male rats were randomly divided into three groups: sham operation group, T3 group, IR group and IR T3 group. Thyroid hormone 10 ug/100 g was injected intraperitoneally in group T3 and IR group 6 h after reperfusion, and the other two groups were injected with the same amount of normal saline respectively. At 24 hours after anaesthesia, the rats were graded according to Longa5 score and brain tissues were taken after 24 h reperfusion. The area percentage of cerebral infarction in rats was detected by using the method of 2ttriphenyl 5-triphenyltetrazolium chloride,TTC staining, and the pathological structure of brain tissue was observed by HE staining. The expression of NF- 魏 B mRNA,TNF- 偽 mRNA in ischemic cortex of rats was detected by real-time fluorescence quantitative PCR (Real-Time PCR), and the expression of NF- 魏 B mRNA,TNF- 偽 protein in ischemic cortex was detected by immunohistochemical staining. Results the scores of neurological function and the percentage of cerebral infarction area in 1.IR T3 group were significantly lower than those in IR group (P0.05). The results of 2.HE staining showed that the pathological damage of brain tissue in IR T3 group was significantly less than that in IR group. Real-time PCR and immunohistochemical results showed that, There was no significant difference in the expression of NF- 魏 B mRNA,TNF- 偽 mRNA and its protein in ischemic cortex between sham-operated group and T3 group. Compared with sham operation group, the expression of NF- 魏 B mRNA,TNF- 偽 mRNA and its protein in ischemic cortex of IR group was significantly increased (P0.05). Compared with IR group, the expression of NF- 魏 B mRNA,TNF- 偽 mRNA and its protein decreased significantly in IR T3 group (P0.05). Conclusion 1. Thyroid hormone has protective effect on cerebral ischemia-reperfusion injury in rats. 2. The protective effect of thyroid hormone is achieved by down-regulating the expression of inflammatory factor NF- 魏 B, TNF- 偽.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743
[Abstract]:Background Ischemic cerebrovascular disease (ICVD) is a kind of three high diseases with high morbidity, high disability rate and high mortality rate. It is a serious threat to human health and affects the quality of life. In recent years, the treatment of ischemic cerebrovascular disease mainly includes arteriovenous thrombolysis, mechanical thrombolysis and so on. The main purpose is to recanalize the blood flow and save the ischemic penumbra in time. Although the tissue cells can get fresh blood flow again and avoid further ischemia and hypoxia after vascular recanalization, the problem of ischemia reperfusion injury is also the most prominent and hot issue at present. Ischemia-reperfusion injury refers to the new injury of tissue and organ after the tissue regains blood flow. Ischemia-reperfusion injury involves a variety of complex pathological processes, inflammatory response is one of the important pathological mechanisms involved, and the final result can lead to the death of neurons. The expression of nuclear factor-kappa BNF- 魏 B), tumor necrosis factor (tumor necrosis factor,TNF- 偽) is easy after cerebral ischemia, which can be used as an index to simulate the pathophysiological process of cerebral ischemia in human body. Thyroid hormones are known to have an important effect on the development of the central nervous system. However, there are few reports about the effect of thyroid hormone on ischemia reperfusion injury (Ischemic-reperfusion,IR). The effect of thyroid hormone (Triiodothyronine,T3) on the expression of inflammatory factor NF- 魏 B (TNF- 偽) in rats with middle cerebral artery occlusion (MCAO) was studied. To explore the role of thyroid hormone in inflammatory response pathway and provide a new idea for the treatment of cerebrovascular disease. Objective to investigate the effect of thyroid hormone (T 3) on the expression of NF- 魏 B tNF- 偽 in ischemic cortex of rats after cerebral ischemia reperfusion injury (IR). Methods 96 healthy adult SD male rats were randomly divided into three groups: sham operation group, T3 group, IR group and IR T3 group. Thyroid hormone 10 ug/100 g was injected intraperitoneally in group T3 and IR group 6 h after reperfusion, and the other two groups were injected with the same amount of normal saline respectively. At 24 hours after anaesthesia, the rats were graded according to Longa5 score and brain tissues were taken after 24 h reperfusion. The area percentage of cerebral infarction in rats was detected by using the method of 2ttriphenyl 5-triphenyltetrazolium chloride,TTC staining, and the pathological structure of brain tissue was observed by HE staining. The expression of NF- 魏 B mRNA,TNF- 偽 mRNA in ischemic cortex of rats was detected by real-time fluorescence quantitative PCR (Real-Time PCR), and the expression of NF- 魏 B mRNA,TNF- 偽 protein in ischemic cortex was detected by immunohistochemical staining. Results the scores of neurological function and the percentage of cerebral infarction area in 1.IR T3 group were significantly lower than those in IR group (P0.05). The results of 2.HE staining showed that the pathological damage of brain tissue in IR T3 group was significantly less than that in IR group. Real-time PCR and immunohistochemical results showed that, There was no significant difference in the expression of NF- 魏 B mRNA,TNF- 偽 mRNA and its protein in ischemic cortex between sham-operated group and T3 group. Compared with sham operation group, the expression of NF- 魏 B mRNA,TNF- 偽 mRNA and its protein in ischemic cortex of IR group was significantly increased (P0.05). Compared with IR group, the expression of NF- 魏 B mRNA,TNF- 偽 mRNA and its protein decreased significantly in IR T3 group (P0.05). Conclusion 1. Thyroid hormone has protective effect on cerebral ischemia-reperfusion injury in rats. 2. The protective effect of thyroid hormone is achieved by down-regulating the expression of inflammatory factor NF- 魏 B, TNF- 偽.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743
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相關(guān)期刊論文 前10條
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