本文選題：靜脈血栓栓塞癥 + 可溶性纖維蛋白復(fù)合物　； 參考：《大連醫(yī)科大學(xué)》2012年碩士論文

【摘要】：研究背景及目的靜脈血栓栓塞癥（Venous Thromboembolism, VTE）包括深靜脈血栓形成（Deep Venous Thrombosis, DVT）和肺血栓栓塞癥（PulmonaryThromboembolism, PTE）。DVT和PTE不是兩種獨(dú)立的疾病，而是VTE一個(gè)連續(xù)過程。臨床確診VTE的方法主要依靠CT肺動脈造影、放射性核素肺通氣/血流灌注掃描、磁共振血管造影及肺動脈造影等影像學(xué)檢查，至今上述檢查不僅仍未普及，而且對于重癥或特殊體質(zhì)患者也存在禁忌。因此，尋找一種早期敏感性和特異性高、簡便易行且費(fèi)用低廉的血漿標(biāo)志物成為關(guān)鍵問題。 本研究通過建立大鼠靜脈血栓栓塞癥模型，動態(tài)檢測大鼠血漿中凝血-纖溶標(biāo)記物——可溶性纖維蛋白復(fù)合物（SFC）、凝血因子ⅩⅢ (FⅩⅢ)和D-二聚體(D-dimer)的水平變化，深入理解VTE的病理生理過程以及上述凝血-纖溶標(biāo)記物的作用和意義。 材料和方法Sprague-Dawley大鼠18只，雌雄各半，隨機(jī)分為DVT組、DVT-PTE組、假手術(shù)（Sham）組，每組6只。用微型血管夾阻滯左側(cè)股靜脈血流制備DVT模型，DVT造模成功后3天取出左側(cè)股靜脈栓子，從右側(cè)股靜脈注入，制備PTE模型。假手術(shù)組只分離左側(cè)股靜脈。造模成功后，分別于栓塞前（0h）和栓塞后不同時(shí)間點(diǎn)（3hs、6hs、12hs、1d、2ds、3ds）采血，應(yīng)用酶聯(lián)免疫吸附法（ELISA法）測定各組栓塞前和栓塞后不同時(shí)間點(diǎn)大鼠血漿中SFC、FⅩⅢ和D-dimer的水平，描繪各項(xiàng)標(biāo)志物的濃度-時(shí)間柱形圖及濃度-時(shí)間線圖，應(yīng)用計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差表示，使用配對t檢驗(yàn)，對栓塞后和栓塞前的各項(xiàng)指標(biāo)進(jìn)行統(tǒng)計(jì)學(xué)分析，組間分析采用單因素方差分析，P0.05為差異具有統(tǒng)計(jì)學(xué)意義。 結(jié)果 1.血漿SFC水平 DVT組：SFC水平在2ds達(dá)峰值（19.795±9.626ug/ml），與0h（4.108±0.809ug/ml）比較，差異具有統(tǒng)計(jì)學(xué)意義（t=2.923，P=0.033），至第3天恢復(fù)正常水平。 DVT-PTE組：SFC水平在3hs即達(dá)峰值22.643±19.417ug/ml，但與栓塞前（5.192±0.338ug/ml）相比，差異無統(tǒng)計(jì)學(xué)意義（t=2.213，P=0.078），至第2-3天仍維持較高水平（11.212±12.742ug/ml；11.138±11.839ug/ml，但與栓塞前比較差異無統(tǒng)計(jì)學(xué)意義（t=1.147，P=0.303；t=1.216，P=0.278）。 Sham組：SFC水平在3h即開始升高（17.816±4.702ug/ml），至12hs時(shí)達(dá)峰值（24.322±1.101ug/ml），與0h（3.698±0.676ug/ml）比較，差異均具有顯著性（t=6.607，P=0.007；t=43.729，P=0.000），至第3天恢復(fù)正常水平。 2.血漿FⅩⅢ水平 DVT組：FⅩⅢ水平在6hs達(dá)峰值（557.685±473.435ng/ml），與0h（77.563±22.949ng/ml）比較，，差異具有統(tǒng)計(jì)學(xué)意義（t=3.204，P=0.029），至第3天仍維持較高水平（291.523±206.034ng/ml），但與栓塞前比較差異無統(tǒng)計(jì)學(xué)意義（t=2.259，P=0.073）。 DVT-PTE組：FⅩⅢ水平在3hs即達(dá)峰值（638.716±674.793ng/ml），但與栓塞前（242.180±26.282ng/ml）相比，差異無統(tǒng)計(jì)學(xué)意義（t=1.449，P=0.207）。 Sham組：FⅩⅢ水平在術(shù)后2ds達(dá)峰值（554.295±180.036ng/ml），與術(shù)前（94.716±13.475ng/ml）相比，差異具有統(tǒng)計(jì)學(xué)意義（t=5.517，P=0.012），至第3天仍維持較高水平（398.217±214.255ng/ml），但與栓塞前比較差異無統(tǒng)計(jì)學(xué)意義（t=2.670，P=0.076）。 3.血漿D-dimer水平： DVT組：D-dimer水平在6hs達(dá)峰值（353.380±74.235ng/ml），與0h（40.316±4.345ng/ml）相比，差異具有統(tǒng)計(jì)學(xué)意義（t=2.298，P=0.03），24小時(shí)仍維持較高水平（229.159±181.274ng/ml），與0h比較，差異具有顯著性（t=2.995，P=0.02），至第3天恢復(fù)正常水平。 DVT-PTE組：D-dimer水平在12-24hs升高并達(dá)峰值（476.576±317.067ng/ml；481.177±322.763ng/ml），與栓塞前（55.785±10.489ng/ml）比較，差異均具有統(tǒng)計(jì)學(xué)意義（t=3.18，P=0.025；t=3.159，P=0.025）。至第2-3天仍維持較高水平（382.956±341.929ng/ml，381.943±346.108ng/ml），但與栓塞前比較差異無統(tǒng)計(jì)學(xué)意義（t=2.361，P=0.065；t=2.327，P=0.067）。 Sham組：D-dimer水平術(shù)后3hs即升高（450.881±165.966ng/ml），24hs達(dá)高峰（504.488±124.615ng/ml），與術(shù)前（51.050±6.795ng/ml）相比，差異均具有顯著性（t=6.071，P=0.000；t=9.170，P=0.000）。2-3天恢復(fù)正常水平。 結(jié)論 1.凝血-纖溶標(biāo)志物——血漿SFC、FⅩⅢ和D-dimer水平的升高是實(shí)驗(yàn)性VTE的早期敏感指標(biāo)，并呈動態(tài)變化，但并非特異。 2.DVT和PTE作為VTE的不同階段，凝血-纖溶標(biāo)志物的表達(dá)不盡相同，DVT是SFC在FⅩⅢ交聯(lián)作用下血栓形成，并同時(shí)被溶解的動態(tài)過程；而PTE則以栓子栓塞后不斷溶解過程為主，盡管SFC和FⅩⅢ有升高趨勢，但與栓塞前比較差異無顯著性。 3.手術(shù)創(chuàng)傷可導(dǎo)致凝血-纖溶標(biāo)志物——血漿SFC、FⅩⅢ和D-dimer水平的升高，是VTE的易患因素。
[Abstract]:Background and objective Venous Thromboembolism (VTE) includes deep venous thrombosis (Deep Venous Thrombosis, DVT) and pulmonary thromboembolism (PulmonaryThromboembolism, PTE).DVT and PTE are not two independent diseases, but a continuous process of VTE. Radionuclide pulmonary ventilation / perfusion scan, magnetic resonance angiography and pulmonary arteriography are not only still not popularized, and there are also taboos for patients with severe or special physique. Therefore, looking for a kind of early sensitivity and specificity, easy and inexpensive plasma markers become a close. Key problem.
In this study, a rat model of venous thromboembolism was established to dynamically detect the levels of coagulation fibrinolytic markers, soluble fibrin complex (SFC), coagulation factor III (F III) and D- two polymer (D-dimer) in rat plasma, and to understand the pathophysiological process of VTE and the role and meaning of the above coagulation fibrinolytic markers. Righteousness.
Materials and methods 18 Sprague-Dawley rats, male and female, were divided randomly into group DVT, group DVT-PTE, sham operation (Sham) group, 6 in each group. DVT model was prepared by blocking the left femoral vein blood flow with microvascular clamp. The left femoral vein embolus was taken out 3 days after the success of DVT modeling, and the PTE model was prepared from the right femoral vein. The sham operation group only separated the left femoral statics. Blood samples were collected at different time points before embolism (0h) and after embolization (3hs, 6HS, 12hs, 1D, 2ds, 3ds) after embolization. The levels of SFC, F, III and D-dimer were measured by enzyme linked immunosorbent assay (ELISA method) in each group of rats before and after embolization. The concentration time column diagram and concentration time line were depicted. The measurement data were expressed with mean standard deviation, and paired t test was used to analyze the indexes of post embolism and pre embolism. The analysis between groups was analyzed by single factor analysis of variance, and the difference of P0.05 was statistically significant.
Result
1. plasma SFC level
Group DVT: the level of SFC was at the peak of 2ds (19.795 + 9.626ug/ml). Compared with 0h (4.108 + 0.809ug/ml), the difference was statistically significant (t=2.923, P=0.033), and the normal level was restored to third days.
Group DVT-PTE: the level of SFC was 22.643 + 19.417ug/ml at 3hs, but there was no statistically significant difference (t=2.213, P=0.078) compared with before embolization (t=2.213, P=0.078), and still maintained a high level (11.212 + 12.742ug/ml, 11.138 + 11.839ug/ml) on day 2-3, but there was no significant difference from before embolism (t=1.147, P=0.303; t=1.216,).
Group Sham: the level of SFC began to rise at 3H (17.816 + 4.702ug/ml) and reached a peak (24.322 + 1.101ug/ml) at 12hs. Compared with 0h (3.698 + 0.676ug/ml), the difference was significant (t=6.607, P=0.007; t=43.729, P=0.000), and recovered to the normal level to third days.
2. plasma F level III level
Group DVT: the level of F III was peak at 6HS (557.685 + 473.435ng/ml). Compared with 0h (77.563 + 22.949ng/ml), the difference was statistically significant (t=3.204, P=0.029), and still maintained a high level (291.523 + 206.034ng/ml) to third days, but there was no statistical significance (t=2.259, P=0.073) before the embolism.
Group DVT-PTE: the level of F III was peak at 3hs (638.716 + 674.793ng/ml), but there was no statistically significant difference compared with that before embolization (242.180 + 26.282ng/ml) (t=1.449, P=0.207).
In group Sham, the peak value of F III was peak (554.295 + 180.036ng/ml) after operation. Compared with preoperative (94.716 + 13.475ng/ml), the difference was statistically significant (t=5.517, P=0.012), and still maintained a high level (398.217 + 214.255ng/ml) to third days, but there was no statistical difference compared with before embolization (t=2.670, P=0.076).
3. plasma D-dimer level:
Group DVT: the peak value of D-dimer was at the peak of 6HS (353.380 + 74.235ng/ml). Compared with 0h (40.316 + 4.345ng/ml), the difference was statistically significant (t=2.298, P=0.03) and still maintained a high level (229.159 + 181.274ng/ml) for 24 hours. Compared with 0h, the difference was significant (t= 2.995, P=0.02), and recovered to the normal level to third days.
Group DVT-PTE: the level of D-dimer increased at 12-24hs and reached its peak value (476.576 + 317.067ng/ml; 481.177 + 322.763ng/ml). The difference was statistically significant (t=3.18, P=0.025; t=3.159, P=0.025) compared with before embolization (t=3.18, P=0.025; t=3.159, P=0.025). To the 2-3 day, the difference was still high (382.956 +, 381.943 + 346.108ng/ml), but with embolism. The difference was not statistically significant (t=2.361, P=0.065; t=2.327, P=0.067).
Group Sham: after D-dimer level, 3hs increased (450.881 + 165.966ng/ml) and 24hs reached a peak (504.488 + 124.615ng/ml). Compared with preoperative (51.050 + 6.795ng/ml), the difference was significant (t=6.071, P=0.000; t=9.170, P=0.000).2-3 days resumed normal levels.
conclusion
1. elevated coagulation fibrinolytic markers, plasma SFC, F III and D-dimer levels, are early sensitive indicators of experimental VTE, and are dynamic, but not specific.
2.DVT and PTE are different stages of VTE, and the expression of coagulation and fibrinolytic markers is not the same. DVT is a dynamic process of thrombus formation and simultaneous dissolution of SFC under the cross linking of F III. While PTE has been dissolved mainly after embolic embolism, although SFC and F III have a higher trend, but there is no significant difference from before embolism.
3. surgical trauma can lead to elevated coagulation and fibrinolytic markers, plasma levels of SFC, F, III and D-dimer, and is a predisposing factor for VTE.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R563.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 李圣青,張艱,戚好文,楊貴忠;小鼠肺栓塞模型的誘導(dǎo)及比較[J];第四軍醫(yī)大學(xué)學(xué)報(bào);2004年15期

2 季穎群,高鶴立,張中和;家兔自體血凝塊制備肺栓塞模型的探討[J];實(shí)驗(yàn)動物科學(xué)與管理;2001年04期

3 宋g

本文編號：1869817