Studies On The Anti-inflammatory Action Of DhHP-6

Inflammation is the defensive response of living organisma to tissue damage or infection. Only the organisms possess circulatory system can generate inflammation. The response is characteristic as vascular leakage and is a multi-biologic process refers to immune system body fluid and cells. Study found that inflammation had close relationship with lots of important clinical diseases such as asthma, cancer, Alzheimer's disease, cardiovascular and cerebrovascular diseases, type II diabetes.Free radicals are atoms and molecules with only one unpaired outer orbital electron. Reactive oxygen species (ROS) are considered as a group of active substances containing oxygen, including oxygen radicals.Many researchers found that ROS and inflammation were closely related. ROS could promote inflammation by direct action or by regulating the expression of certain genes.Many polypeptides are shown anti-inflammation effect. Musk polypeptides can inhibit capillary permeability intension. MCD peptides can inhibit carrageenan induced hind paw edema. Keratin polypeptides cause the inhibition of both histamine or the acetic acid induced capillary permeability intension and cotton-ball granuloma.In our previous work, we designed and synthesized a novel peroxidase mimics called Deuterohaemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6). DhHP-6 can simulate the activity of MP-11 pretty well in vitro, having a powerful rule of scavenging ROS. Besides DhHP-6 has very good water solubility, stability and its chemical synthesis is much more simple. So DhHP-6 can be chosen as a potential anti-inflammation drug to research.In the papers the anti-inflammatory effect of DhHP-6 was observed through the dimethylbenzene induced ear swelling response in mice, the acetic acid induced capillary permeability intension in mice, the egg albumin-induced hind paw edema in rats and the carrageenan induced acute air-pouch synovitis in rats. The analgesic effect of DhHP-6 was observed through the HAC induced writhing in mice. Experimental animals were divided into groups respectively as follows:control group; therapeutic drug treated group and three dozes of DhHP-6 treated groups. The dozes of DhHP-6 treated mice were 0.3mg/kg,1mg/kg and 3mg/kg, while in rats the dozes were 0.2mg/kg,0.6mg/kg and 2mg/kg, intraperitoneal injection. Researching the experimentation of imethylbenzene induced ear swelling response in mice, discovered that high dose of DhHP-6 (3mg/kg) can apparently inhibit the swelling degree (P< 0.05), the inhibiton ratio was 44.7%. Researching the experimentation of the HAC induced capillary permeability intension in mice discovered that high dose of DhHP-6 (3mg/kg) can inhibit the intension of capillary permeability leaded by HAC obviously, contrast to control group, P<0.05. The inhibiton ratio was 44.7%. Researching the experimentation of the egg albumin-induced hind paw edema in rats indicated:high dose of DhHP-6 can inhibit the swelling degree in 2h after egg albumin was administrated. DhHP-6 could decrease the leucocytes and protein in the diffusate in air-pouch synovitis rats (P<0.05). The above conclusions explain that DhHP-6 can antagonize vessels extension, the intensification of capillary permeability and neutrophilic granulocyte and protein exudation. DhHP-6 can not reduce the number of mice writhing induced by HAC. We can conclude that DhHP-6 has anti-inflammatory effect, however the analgesic effect is not ideal.PGE2 is an important inflammation mediator. Many anti-inflammatory drugs such as aspirin and glucocorticoids show anti-inflammation activity by inhibiting the synthesis of PGE2. It is able to dilate blood vessels, and increase capillary permeability then induce edema. Previous researchers found increased content of PGE2 in the blood of air-pouch synovitis rats. Researching studies of carrageenan induced acute air-pouch synovitis in rats discovered that high dose of DhHP-6 can reduce the PGE2 in the blood of air-pouch synovitis rats.It maybe the cause that DhHP-6 can decrease the leucocytes and protein in the diffusate in air-pouch synovitis rats. Researches also found DhHP-6 could reduce the expression of important cytokines TNF-αand IL1-β. This maybe another reason that DhHP-6 has anti-inflammatory effect.We had a simple research on the anti-inflammatory effect of DhHP-6 results demonstrate that DhHP-6 has some anti-inflammatory effect. DhHP-6 can depress ear-swelling induced by xylal and the edema of rat hind paw induced by egg, inhibit capillary permeability intension induced by the acetic acid, reduce the contents of white cells and protein in the exudate of acute air-pouch synovitis rats induced by carrageenan. DhHP-6 can improve anti-oxygenize level by improve the activity of SOD and reduce content of MDA. DhHP-6 can inhibite the synthesis of PGE2 and the expression of TNF-α, IL1-β. The datas presented in this thesis have provided a framework and a basis for further investigation.