Clinical studies on coagulation and fibrinolysis have been only confined to blood samples over a long period of time. However, the factors in blood participating in coagulation and fibrinolysis are all from cell secretions so that the activities of coagulation and fibrinolysis in tissues which present the biological characteristics of tissues become an indispensable element in physiological coagulation and fibrinolysis, and especially, are closely associated with the behavior of tumor (Casslen et al., 1994; Schmitt et al., 2006; Zekanowska et al., 2004; Lu et al., 2003; Hatton et al., 2006). Because the abnormality of fibrinolysis detected by serum tests is correlated with the imbalance between fibrinolytic factors and their inhibitors excreted by local lesion or cells (Gesualdo et al., 1999; Kurose et al., 1992; Stenberg et al., 1983), hence, investigating fibrinolysis from other aspects such as its role in tissues is helpful for revealing the pathophysiologic mechanism of various diseases. Our present work aims to elucidate the distribution pattern of fibrinolytic factors and their inhibitors in rabbit tissues extract through determining their activities.

There may be some interrelationships between thrombosis or haemorrhage and the levels of fibrinolytic factors and their inhibitors in tissues. As far as clinical pathological mechanism was concerned, in addition to its role in degradation of extracellular matrix, fibrinolysis in tissues may participate in tumor invasion and be related with other diseases. For instance, PAI-1 in renal glomerulus induced by angiotensin IV in peritubular epithelial cells is related with occurrence of interstitial fibrosis in chronic nephritis (Gesualdo et al., 1999). Increased expression of PAI-1 had been detected in normal migrating cells and in metastasizing tumor cells (Sumiyoshi et al., 1991; Liu et al., 1994). Overexpression of PAI-1 protein was observed at the invasive front of breast cancer tissue specimens (Umeda et al., 1997). While in mucosa of peptic ulcer and ulcerative colitis, the activity of fibrinolysis evidently increased, with the latter also being pertinent to the degree of inflammation (Kurose et al., 1992). In addition, previous study had already shown that the gastrointestinal pathological changes may be ameliorated through therapy against fibrinolysis (Stenberg et al., 1983).

Our study found that the expression patterns of fibrinolytic factors and their inhibitors were different in various rabbit tissues extract. Some organs such as kidney, small intestine, lung, brain and spleen presented significantly higher levels of fibrinolytic factors (tPA, Plg and Pl), and lower fibrinolytic inhibitors (PAI-1 and α₂PI), while in skeletal muscle, tongue and stomach, the matter was just the reverse. So, the results indicated there was a diversity of fibrinolysis in these tissues. Furthermore, we found that a negative correlation existed in tPA and PAI-1, Pl and α₂PI, respectively, and a positive correlation between Plg and Pl. Meanwhile, analysis of the ratio of Pl to α₂PI, tPA to PAI-1 and Plg to Pl showed that a different intensity and proportion of fibrinolysis distributed in these tissues. For example, a higher ratio of tPA to PAI-1 appeared in renal cortex and renal marrow, whereas in skeletal muscle and tongue the ratio was lower. Those results reflected the fibrinolytic levels of rabbit in the normal condition and were helpful for evaluating the fibrinolysis condition of tissues and the susceptibility of haemorrhage during operation.

To our great surprise, there were many interesting direct ratios and inverse ratios of fibrinolytic factors to their inhibitors in some related tissues. For instance, the tPA level was higher and the PAI-1 level was lower in renal cortex and renal marrow; the Plg and Pl levels were higher in renal cortex than those in renal marrow, and the α₂PI was higher in renal marrow than that in renal cortex. The levels of fibrinolytic factors were higher in small intestine than those in large intestine, whereas the fibrinolytic inhibitors in large intestine were more numerous than those in small intestine. Analysis of levels of fibrinolytic factors and their inhibitors in gastrointestinal mucosa and submucosa revealed that higher activities of tPA and Pl are present in mucosa of large intestine and small intestine compared to in submucosa, which implied that the function of fibrinolysis in intestine is chiefly located in submucosa. Hence, we suggest that fibrinolytic factors and their inhibitors may participate in some gastrointestinal mucosa pathological changes in given condition, consistent with certain work in other clinical trials (Kurose et al., 1992; Stenberg et al., 1983). Kurose et al.(1992) also found the mucosa lesion in ulcerative colonitis was often linked to its aberrant fibrinolysis. Padro et al.(1994) investigated the relationship of the layers of rat aorta with fibrinolysis and subsequently confirmed that tPA activity and tPA antigen were detected in the intima-media and tunica adventitia, whereas in the tunica media only PAI-1 activity showed, no tPA activity was detected. This distribution pattern enabled us to obtain extraordinary knowledge about the fibrinolysis, coagulation and their inhibitors in tissue. In brain, our results indicated that only tPA level was higher whereas fibrinolytic inhibitors level was lower, thus, the brain showed relatively high activity of fibrinolysis. In addition, it may be an interesting phenomenon that the muscle tissues, such as skeletal muscle, cardiac muscle and tongue, showed lower fibrinolysis activity as well as higher inhibitors activity. However, with regard to muscle tissue, the activity of fibrinolysis in cardiac muscle is obviously stronger than that in skeletal and tongue muscles which also poses a worthwhile question. Consistent with our data, previous study also found the fibrinolytic and coagulant activity in rabbit tissues was similar to that in rat (Lu, 1990). As far as procoagulant active substances and their inhibitors in rabbit tissue extracts are concerned, we observe that a significant heterogeneity in the levels of fibrinolysis, coagulation and their inhibitors is shown in some tissues (Fang et al., 2005). For instance, the levels of fibrinolytic and anticoagulant factors were markedly lower but procoagulant activity increased significantly in muscle tissues, this vivid contrast against each other may be linked to the muscle tissues’ toughness and resistance to autolysis. Although it was difficult to explain what physiological and pathological implications this considerably amazing phenomenon gave, it indeed deserved further investigation. Similarly, the obvious discrepancy between small intestine which showed the higher activities of fibrinolysis and coagulation and large intestine which showed the lower activities of fibrinolysis accorded with the symptoms that hemorrhagic infarct easily appeared in small intestine and hemorrhage in large intestine, suggesting that this discrepancy may be closely linked to their different physiological function. In summary, our interesting data suggest that further studies warrant a rethinking of unexpected properties of fibrinolysis, coagulation and their inhibitors in tissues other than their functions in the blood stream.