本文選題：胰島素　切入點(diǎn)：急性肺損傷　出處：《中南大學(xué)》2012年碩士論文

【摘要】：目的： 研究胰島素(ISL)在脂多糖(LPS)誘導(dǎo)的急性肺損傷(ALI)中的治療作用及其相關(guān)機(jī)制。 方法： 將72只雄性SD大鼠隨機(jī)分為9組,分別為正常對照組、造模組(LPS注射后2h、6h、12h、24h組)、治療組(LPS注射后2h、6h、12h、24h組)。各組均將尾靜脈注射LPS的時間列為實(shí)驗(yàn)時間點(diǎn)“0”,造模組尾靜脈注射LPS4mg/kg,治療組在LPS注射前2h腹部皮下注射中效胰島素4U/kg,正常對照組在相應(yīng)時間和相同部位注射等量生理鹽水。按時取血標(biāo)本測定血糖水平、ELISA法測定血清C肽和肺組織勻漿TNF-α濃度、免疫組織化學(xué)法檢測肺組織中MMP-9和TIMP-1表達(dá)；同時檢測肺濕干重比(W/D)和肺組織病理變化情況。 結(jié)果： 1、與正常對照組相比較,尾靜脈注射LPS4mg/kg后約1小時,SD大鼠出現(xiàn)不同程度的煩躁不安、呼吸急促、活動減少、反應(yīng)遲鈍等表現(xiàn)；2小時后肺W/D增高、肺間質(zhì)水腫、中性粒細(xì)胞浸潤、彌漫性毛細(xì)血管擴(kuò)張、肺泡腔出血、部分肺泡萎陷或肺實(shí)變及氣腫等肺組織急性炎性病理改變,提示采用LPS成功復(fù)制了ALI動物模型。 2、造模組大鼠的血糖和血C肽水平變化呈現(xiàn)相同的趨勢,注射LPS后2h升高,12h達(dá)到最高,之后下降但仍顯著高于正常,提示LPS誘導(dǎo)的ALI存在胰島素抵抗現(xiàn)象。 3、造模組大鼠在注射LPS后2h肺組織勻漿TNF-α水平開始升高,6h達(dá)高峰,之后逐漸下降,24h時仍高于正常對照組(P0.05)；其肺組織中MMP-9和TIMP-1表達(dá)增高且變化趨勢相同,2h升高,12h達(dá)高峰,24h時下降但仍高于正常對照組(P0.05)。 4、與造模組相比較,治療組大鼠病情嚴(yán)重程度和肺組織病理損傷程度明顯減輕,血糖和C肽水平下降,肺組織勻漿TNF-α和肺組織MMP-9表達(dá)水平顯著下降,而肺組織TIMP-1表達(dá)增高、MMP-9/TIMP-1比值下降。 結(jié)論： (1)脂多糖誘導(dǎo)的大鼠急性肺損傷存在胰島素抵抗現(xiàn)象。 (2)胰島素治療有助于減輕脂多糖所致的急性肺損傷,其機(jī)制可能與其對抗胰島素抵抗現(xiàn)象、及降低TNF-α水平、減少M(fèi)MP-9表達(dá)、升高TIMP-1表達(dá)有關(guān)、使MMP-9/TIMP-1體系趨于平衡。
[Abstract]:Objective:. To study the therapeutic effect of insulin ISL on acute lung injury induced by lipopolysaccharide (LPS) and its related mechanism. Methods:. Seventy-two male SD rats were randomly divided into 9 groups as normal control group. The rats in the model group were divided into two groups: 2 h, 6 h, 12 h and 24 h after LPS injection, and 2 h, 6 h, 12 h and 24 h after LPS injection, respectively. The time of intravenous injection of LPS was classified as "0" in each group. The model group was injected with LPS4 mg / kg / L 2 h before LPS injection, and insulin was subcutaneously injected in the treatment group 2 hours before LPS injection. 4U / kg, the normal control group was injected with the same amount of normal saline at the corresponding time and the same part. The blood glucose level was measured by Elisa and the concentration of serum C peptide and lung homogenate TNF- 偽 were determined by Elisa. The expression of MMP-9 and TIMP-1 in lung tissue was detected by immunohistochemical method, and the lung wet / dry weight ratio (WR) and pathological changes of lung tissue were also detected. Results:. 1Compared with the normal control group, the SD rats had different degrees of restlessness, shortness of breath, decreased activity, slow response and so on at 1 hour after LPS4mg/kg injection. After 2 hours, the lung W- / D increased, pulmonary interstitial edema and neutrophil infiltration were observed in SD rats. Diffuse capillary dilatation, alveolar cavity hemorrhage, partial alveolar collapse or pulmonary consolidation, emphysema and other acute inflammatory pathological changes of lung tissue, which indicated that the animal model of ALI was successfully reproduced by LPS. 2. The changes of blood glucose and C-peptide levels in the model group showed the same trend, and reached the highest at 2 h after LPS injection, then decreased significantly but still significantly higher than normal, suggesting that ALI induced by LPS had insulin resistance. 3. The TNF- 偽 level of lung homogenate in the model group began to increase at 2 h after injection of LPS and reached the peak at 6 h. After 24 hours, the expression of MMP-9 and TIMP-1 in the lung tissue of the control group was still higher than that of the normal control group, and the expression of MMP-9 and TIMP-1 in the lung tissue increased at 12 h and reached the peak at 12 h, but was still higher than that of the normal control group at 24 h, but still higher than that of the normal control group. 4Compared with the model group, the severity of the disease and the degree of pathological injury of lung tissue in the treatment group were obviously alleviated, the levels of blood glucose and C-peptide were decreased, and the expression of TNF- 偽 and MMP-9 in the lung homogenate was significantly decreased in the treatment group. However, the ratio of MMP-9 / TIMP-1 decreased when the expression of TIMP-1 in lung tissue increased. Conclusion:. 1) Insulin resistance was found in acute lung injury induced by lipopolysaccharide in rats. 2) Insulin therapy can alleviate acute lung injury induced by lipopolysaccharide, and its mechanism may be related to its resistance to insulin resistance, decrease of TNF- 偽 level, decrease of MMP-9 expression, increase of TIMP-1 expression, and balance of MMP-9/TIMP-1 system.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R563.8

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