敗血症大鼠腦皮層血流的變化及熱休克前處置之影響

敗血病及其併發症如休克、多器官衰竭等，目前仍是最主要造成重症加護病房病人死亡的原因。文獻指出，敗血病導致的多重器官衰竭中，以腦部病變為最早期之徵象，臨床病人呈現意識不清的狀態，目前為止，關於致病的機制尚未釐清。文獻報告指出會導致敗血性腦病變的因素：腦膿瘍（brain microabscesses）、胺基酸（amino acid）代謝不平衡、腦中的神經傳導物質失調與腦血流降低等因素。有學者指出在敗血症早期就會發生血液循環功能不全（microvascular dysfunction）的現象。在本實驗室之前的研究發現，給予大白鼠熱休克前的處置，不但可以降低敗血症的死亡率，另外在缺氧的動物模式下，或給予藥物誘發癲癇時，皆是呈現保護大腦皮質的功能，但目前對於熱休克前處置對腦皮質功能的保護機制仍是尚未清楚。在本實驗中，我們利用Spraque-Dawley (SD)雄性大白鼠，經由靜脈注射內毒素（30 mg/kg），誘發敗血病的動物模式。實驗動物分為三組：1. 未受處置的控制組、2. 誘發敗血病的內毒素組經由靜脈注射內毒素（30 mg/kg）、3. 誘發敗血病的熱休克處置組，熱休克前處置後經由靜脈注射內毒素（30 mg/kg），隨後以微血管顯微攝影，偵測三組大白鼠腦部血流的變化，並將大白鼠犧牲，以光學顯微鏡觀察組織的變化。結果顯示，在給予內毒素的刺激下，在動脈血管，特別是直徑10-30um的血管，內毒素組其直徑收縮且血流速度有減緩的現象，而熱休克處置組則無顯著性差異。靜脈血管分析，血管直徑 > 10 um，內毒素組的血流速度也有呈現明顯的減緩。微血管區內毒素組其微血管灌流功能（functional capillary density）下降，而熱休克處置組無顯著性差異。在組織型態上，可以在內毒素組的靜脈血管內和腦實質組織看到紅血球及纖維蛋白的堆積；而在動脈血管內則無。我們推論熱休克前處置可以透過減少靜脈中血栓的形成改善血管血流速率及血流量，進而保護腦皮質功能，呈現扮演保護性角色。

關鍵字

腦皮層血流；熱休克

並列摘要

Systemic sepsis and its consequences are the commonest cause of death in intensive care units (ICU). The CNS is the first organ system to manifest the functionally depressive effect during sepsis. Septic patients commonly demonstrate mental status changes ranging from mild confusion to coma. Brain microabscesses, disordered amino acid metabolism, alterations in brain neurotransmitters, and reduced cerebral blood flow and oxygen utilization have all been proposed as potential etiologies of septic encephalopathy. Early in sepsis, the inability of the mirovasculature to compensate for a loss of function capillary density is the critical factor that leads to tissue hypoxia and thus organ dysfunction. In our previous study, we showed that heat shock(HS) pretreatment reduced mortality rate in septic rats, and protected the cortical function in hypoxia or drug-induced convulsion. We hypothized that heat shock pretreatment may attenuate the severity of microvascular dysfunction induced by LPS. Male Spraque-Dawley(SD) rats were used as the experimental animal and randomized to e sham, Lipopolysaccharide (LPS) and Heat shock pretreatment with LPS injection groups. LPS and heat shock pretreatment animals received LPS 30mg/kg/iv. Orthogonal polarization spectral(OPS) imaging technique was used to evaluate microvascular blood flow alterations in rats. Our data showed that the velocity of blood flow was reduced and the vessel diameter decreased in most of arterioles(10-30 um) in diameter within one hour after injection of LPS. However, the heat shock pretreatment group reversed the effect in most of the vessels studied. In histological observation, RBC and fibrin accumulated in veinules of tissue treated by LPS. The phenomenon significantly decreased in heat shock pretreatment group. In conclusion, the data suggest heat shock pretreatment improved the blood flow velocity, vessel diameter and might contribute to preserving the cortical dysfunction induced by LPS injection.

並列關鍵字

cortical microcirculation ； Heat shock

參考文獻

Altura BM, 1997. Chemical and humoral regulation of blood flow throughe precapillary sphincter. Microvasc 3：361-84.

Google Scholar

Astiz ME, Rackow EC. 1998. Septic shock. Lancet 351: 1501-1505.

Google Scholar

Bone RC, Grodzin CJ, Balk RA. 1997. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest 112: 2077-2083.

Google Scholar

Bone RC. 1991. The pathogenesis of sepsis. Ann Intern Med 115: 457-469.

Google Scholar

Brown IR, and Rush SJ, 1990. Expression of heat shock genes (hsp70) in the mammalian brain: distinguishing constivutively expressed and hyperthermia-inducible mRNA species. J Neurosic Res 25:14-19.

Google Scholar

國際替代計量

敗血症大鼠腦皮層血流的變化及熱休克前處置之影響

全文下載

主題瀏覽