| Background and purpose Intracerebral Hemorrhage (ICH) is a severe type among cerebral vascular diseases with high occurrence, mortality and mutilation. It markedly threatened human health and imposed heavy burden on society and families. ICH can be categorized into a range of illnesses of "attacked by the factor Feng" in terms of traditional Chinese medicine, which resulted in "extravasated Blood that can not return to former channel". The theory "extravasated Blood being stagnated in head" supports that a status of Blood stagnation plays a key role in hemorrhagic stroke. We used Nao Yi An granule which assigned Da Huang (Radix et Rhizoma Rhei) as a main herb of formula in treatment of ICH and observed positive efficacy. Da Huang has a effect of "dispersing stagnation of Blood" in view of TCM. Modern research in laboratory indicated that Da Huang improved blood circulation and accelerated absorption of hemorrhage. It is clear now that the cerebral tissue of impaired area (inside and around hematoma) has remarkable ischemia and hypoxia hence damages the blood brain barrier (BBB). In addition to the effect of bettering the micro-environment, the application of Nao Yi An granule can improve the ischemia and hypoxia in impaired tissue and extenuate the permeability of BBB hence to provide better condition for injury repair. Zonula occludens-1(ZO-1) exists as one of main proteins constituting the close linkage of blood brain barrier. Its expression largely depends on whether or not the status of BBB is over-exchanging. The normal expression of ZO-1 is associated with stability of inter-cellular linkage and integrality of cellular function. Recent studies on expression of the protein largely focused on cerebral ischemia model in vitro. The present experiment was conducted to explore in vivo the peptides and mRNA expression in intra-cerebral impaired area of ICH rats in addition to the repair on BBB morbidity, which may provide a pilot study helping the understanding on mechanism of rehabilitating effect on BBB of DA Huang.Methods One hundred and ninty male Sprague-Dawley rats were randomly allocated into 4 groups:pseudo-operation, model, Da Huang and healthy control. Indexes on 6 time point assigned 10 rats of each:1d, 2d,3d,5d,7d and 14d, were measured respectively.â…¦-type thrombin was injected into globus pallidus by solid location to fabricate ICH models. Intra-gastric administration of Da Huang was given to rats allocated in Da Huang group whereas distilled water was given to pseudo-operation and model groups. Evans Blue (EB) was used as tracking agent to observe the degree of impairment of BBB on each time point. The expression of ZO-1 on the corresponding time point was tested by Immuohistochemical method.Results 1) the expression of ZO-1 in rats of Da Huang and model groups was significantly lower than that in rats of pseudo-operation group (P<0.01); 2) ZO-1 was expressed the least on the time of 3d in rats of Da Huang and model groups and then gradually increased in further days. Comparing with pseudo-operation rats, the ZO-1 expression of model rats was significantly elevated on the time of 14d (P<0.05). The expression reached peak on time of 7d of Da Huang group which showed no significant difference (P>0.05) comparing with pseudo-operation group. The difference on 1d,2d and 3d between Da Huang and model groups showed statistical significance (P<0.05) whereas the difference on 5d,7d and 14d all reached stronger statistically significant (P<0.01); 3) the capacity of tracking EB within impaired tissue increased significantly in rats of Da Huang and model groups on 1d after ICH comparing with pseudo-operation group. This reached peak on time of 3d and turned lower afterwards. The difference was without statistical significance on 14d comparing with pseudo-operation group (P>0.05). The EB capacity in impaired area decreased along with timing in rats of Da Huang group. On the time of 5d, the difference comparing with pseudo-operation group lost statistical significance (P>0.05).Conclusions 1) The expression of ZO-1 remarkably decreased in rats after ICH occurrence. The increase of BBB permeability may possibly be associated with the insufficient expression of close-linage protein ZO-1 in vascular endothelial cells.2)Intervention of Da Huang enhances expression of ZO-1 in rats of ICH hence lowers the permeability of BBB, protects cerebral nerve cells and accelerates cerebral tissue recovery from impairment induced by ICH.
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