本文選題：丹酚酸A + 尿源性膿毒血癥　； 參考：《浙江大學(xué)》2017年碩士論文

【摘要】：目的:通過(guò)構(gòu)建腎盂內(nèi)高壓合并感染致急性感染性休克兔模型,模擬臨床腔內(nèi)碎石術(shù)后急性感染性休克過(guò)程,研究丹酚酸A(Sal.A)這一具有顯著的抗氧化作用的水溶性酚酸類(lèi)化合物能否改善急性感染性休克的預(yù)后。方法:動(dòng)物實(shí)驗(yàn):將新西蘭兔隨機(jī)分為ABCD四組,分別將2ml/Kg體重生理鹽水、2ml/Kg體重6*10^8cfu/L標(biāo)準(zhǔn)大腸桿菌、2ml/Kg體重9*10^8cfu/L標(biāo)準(zhǔn)大腸桿菌、2ml/Kg體重12*10^8cfu/L注入兔左側(cè)腎盂,分別監(jiān)測(cè)實(shí)驗(yàn)過(guò)程平均動(dòng)脈壓(MAP)的變化,根據(jù)結(jié)果選擇D組作為急性感染性休克模型。隨后將新西蘭兔隨機(jī)分組為空白對(duì)照組(E0)、標(biāo)準(zhǔn)休克模型組(E1)、丹酚酸A干預(yù)組(E2),按2ml/Kg體重向E0組腎盂注入生理鹽水,向E1、E2組腎盂注入12*10^8cfu/L標(biāo)準(zhǔn)大腸桿菌溶液,并在術(shù)后0.5h按10mg/kg體重向E2靜脈注射Sal.A,在E0、E1組同時(shí)間點(diǎn)注射等量生理鹽水,術(shù)后檢測(cè)兔血清晚期氧化蛋白(AOPP),監(jiān)測(cè)平均動(dòng)脈壓(MAP)并記錄生存時(shí)間。結(jié)果:取術(shù)后2、3、4小時(shí)平均MAP作為基礎(chǔ)MAP,與之相比,A組、B組、C組術(shù)后6小時(shí)內(nèi)平均動(dòng)脈壓均無(wú)明顯差異。D組在術(shù)后6小時(shí)平均動(dòng)脈壓明顯下降。D組術(shù)后3小時(shí)平均動(dòng)脈壓(68.8±9.2mmHg)、4小時(shí)(64.6±7.9mmHg)與基礎(chǔ)MAP(69.9±6.7mmHg)相比無(wú)顯著性差異(P0.05),6小時(shí)平均動(dòng)脈壓(61.4±11.3mmHg)與基礎(chǔ)MAP相比明顯下降(P0.05),8小時(shí)平均動(dòng)脈壓(52.8±8.3mmHg)與之相比有顯著性下降(P0.01)。將術(shù)后MAP小于0.7*基礎(chǔ)MAP的時(shí)間點(diǎn)作為休克時(shí)間,D組休克時(shí)間為8.3±0.8小時(shí),死亡時(shí)間為11.1±1.1小時(shí)。因此,我們將D組作為腎盂內(nèi)高壓伴感染性休克的標(biāo)準(zhǔn)模型。E0組(空白對(duì)照組)術(shù)后血壓無(wú)明顯下降,未出現(xiàn)休克,24小時(shí)100%存活。E1組(休克標(biāo)準(zhǔn)對(duì)照組)6小時(shí)平均動(dòng)脈壓(61.6±10.3mmHg)與基礎(chǔ)MAP(68.9±5.3mmHg)相比明顯下降(P0.05),在術(shù)后8.7±0.8小時(shí)出現(xiàn)休克,術(shù)后11.1±0.9小時(shí)死亡,E2組(藥物干預(yù)組)術(shù)后11小時(shí)MAP(46.8±26.6mmHg)與基礎(chǔ)MAP(62.8±16.5mmHg)相比明顯下降(P0.05),在11.9±1.1小時(shí)出現(xiàn)休克,于13.6±1.7小時(shí)死亡。E2組的休克時(shí)間較E1組顯著延后(P0.05),死亡時(shí)間亦明顯延后(P0.05),提示進(jìn)行早期注射丹酚酸A抗氧化治療在某種程度上能夠延后休克及死亡的發(fā)生時(shí)間。E0組的AOPP在術(shù)后8小時(shí)內(nèi)基本保持穩(wěn)定。E1組的AOPP在術(shù)后2小時(shí)較0小時(shí)有輕度升高,自手術(shù)4小時(shí)以后隨時(shí)間呈明顯下降趨勢(shì)(P0.05)。E2組的AOPP在術(shù)后2小時(shí)較0小時(shí)有輕度降低,4小時(shí)以后呈現(xiàn)輕度下降趨勢(shì)(P0.05),直至術(shù)后8小時(shí)較0小時(shí)方有顯著性降低。以AOPP血清白蛋白(Alb)校正休克過(guò)程中蛋白自血管內(nèi)向組織間隙移動(dòng)對(duì)血清AOPP的影響,發(fā)現(xiàn)E1組AOPP/Alb比值在術(shù)后較E2組呈顯著升高趨勢(shì)。結(jié)論從本研究的平均動(dòng)脈壓變化及生存曲線上來(lái)看,用合適劑量的丹酚酸A早期干預(yù)可以延后休克模型的休克發(fā)生及死亡時(shí)間,在一定程度上有改善預(yù)后的作用。從AOPP及AOPP/Alb比值變化來(lái)看,丹酚酸A早期干預(yù)能夠降低感染性休克過(guò)程中的氧化應(yīng)激水平,減少氧化損傷。
[Abstract]:Objective: to simulate the process of acute septic shock after endovascular lithotripsy by constructing a rabbit model of acute septic shock induced by intrapelvic hypertension and infection. To study whether Salvianolic acid A (Sal.A), a water-soluble phenolic acid compound with significant antioxidant effect, can improve the prognosis of acute septic shock. Methods: animal experiments: new Zealand rabbits were randomly divided into four groups of ABCD, and 2 ml / kg body weight of normal saline 2 ml / kg / kg weight of 610 ^ 8 cfur / L standard Escherichia coli 2 ml / kg body weight 9% 10 ^ 8 cfur / L standard Escherichia coli 2 ml / kg / kg weight of 1210 ^ 8 cfur / L was injected into the left renal pelvis of rabbits. The changes of mean arterial pressure (map) were monitored, and group D was selected as the model of acute septic shock according to the results. Then New Zealand rabbits were randomly divided into blank control group (E0), standard shock model group (E1) and Salvianolic acid A intervention group (E2). Normal saline was injected into the renal pelvis of E0 group according to the weight of 2 ml / kg, and 1210 ^ 8 cful standard Escherichia coli solution was injected into the renal pelvis of E1E 2 group. At 0.5 h after operation, Sal.A was injected into E2 according to 10mg/kg body weight, and saline was injected into E0E 1 group at the same time point. Serum late oxidizing protein (AOPP) was detected, mean arterial pressure (map) was monitored and survival time was recorded. Results: the mean map of 2 hours and 3 hours after operation was taken as the basic MAP.Compared with the mean arterial pressure in group A and group B, there was no significant difference in the mean arterial pressure within 6 hours after operation. The mean arterial pressure in group D decreased significantly at 6 hours after operation. The mean arterial pressure in group D decreased significantly at 3 hours after operation. There was no significant difference in arterial pressure (68.8 鹵9.2 mmHg) for 4 hours (64.6 鹵7.9 mmHg) and basic map (69.9 鹵6.7 mmHg) (P0.05). The mean arterial pressure (61.4 鹵11.3 mmHg) in 6 hours was significantly lower than that in basal map (P0.05). The mean arterial pressure (52.8 鹵8.3 mmHg) in 8 hours was significantly lower than that in basal map (P0.01). The shock time of group D was 8.3 鹵0.8 hours and the time of death was 11.1 鹵1.1 hours. Therefore, we treated group D as the standard model of intrapelvic hypertension with septic shock. Group E0 (blank control group) showed no significant decrease in blood pressure after operation. The mean arterial pressure at 6 hours (61.6 鹵10.3mmHg) and basal map (68.9 鹵5.3mmHg) decreased significantly in the 100% survival group (shock standard control group) without shock at 24 hours (P0.05), and shock occurred at 8.7 鹵0.8 hours postoperatively. Map (46.8 鹵26.6mmHg) decreased significantly in E _ 2 group at 11.1 鹵0.9 hours postoperatively compared with baseline map (62.8 鹵16.5 mmHg) (P0.05), and shock occurred at 11.9 鹵1.1 hours. At 13.6 鹵1.7 hours, the shock time of E2 group was significantly delayed than that of E1 group (P0.05), and the time of death was also significantly delayed (P0.05), suggesting that early anti-oxidation therapy of Salvianolic acid A could delay shock and death to some extent in E0 group. AOPP in group 1 remained stable within 8 hours after operation. AOPP increased slightly at 2 hours after operation compared with 0 hours after operation. AOPP in E2 group decreased slightly after 2 hours compared with 0 hours after operation (P0.05), then decreased slightly after 4 hours (P0.05), and decreased significantly at 8 hours after operation compared with 0 hours after operation (P0.05). AOPP / Alb ratio in E1 group was significantly higher than that in E2 group. Conclusion according to the change of mean arterial pressure and survival curve of this study, early intervention with appropriate dose of Salvianolic acid A can delay the onset and death time of shock in the model of shock, which can improve the prognosis to some extent. According to the changes of AOPP and AOPP / Alb ratio, early intervention of Salvianolic acid A can reduce oxidative stress and reduce oxidative damage during septic shock.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R699
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本文編號(hào)：2094008