Research On The Treatment And Mechanism Of Alpha 1 Antitrypsin On Guinea Pig Skin Photoaging Model

Objectives 1.To establish the animal model of Guinea pig skin photoaging. 2.To observe the prevention and therapeutic effect of AAT on Guinea pig skin photoaging model. 3.To investigate the mechanism of AAT on preventing and treating Guinea pig skin photoaging.Methods 1.sixty female guinea pigs were randomly divided into three groups: blank control group(6 guinea pigs),model group(48 guinea pigs,1 to 2 hours after using 0.1% Methoxsalen Solution, expose the guinea pigs to 20 w UVA and UVB light for 120 hours),prevent group(6 guinea pigs, prepare animal model as the model group and give them AAT 20 mg each animal by intraperitoneal injection every 3 days at the same time). Observe general skin changes and pathological changes. 2.Forty-two guinea pigs of the model group were randomly divided into seven groups: positive control group(6 guinea pigs, use Tretinoin ointment every day), negative control group one(6 guinea pigs, give 0.5ml sterile water every three days through intraperitoneal injection), negative control group two(6 guinea pigs, externally use gel 0.5ml every three days), high-dose treatment group by intraperitoneal injection(6 guinea pigs, give AAT 20 mg every three days by intraperitoneal injection), low-dose treatment group by intraperitoneal injection(6 guinea pigs, give AAT 5mg every 3 days by intraperitoneal injection), high-dose treatment group by external use(6 guinea pigs, externally use AAT 20 mg every three days), low-dose treatment group by external use(6 guinea pigs, externally use AAT5mg every three days). Observe and compare each group through general skin changes and pathological changes. Compare the related cytokines and enzymes of each group and then make statistical analysis.Results 1. 0.1% 8-MOP combined with UVA and UVB exposure add up to 120 hours, skin exposed to ultraviolet radiation shows coarse wrinkles, hyperpigmentation, epidermic thicking, inflammatory cell infiltration, disordered collagen fiber and so on. 2.When the photoaging model was established successfully, compared with that of model group, skin of prevent group shows obvious reduction in general skin changes and pathological findings. 3. Compared with that of model group, skin of high-dose treatment group shows obvious reduction in general skin changes and pathological findings. Skin of low-dose treatment groups also show reduction, but not as good as those of high-dose treatment groups. There’s no apparent difference in the therapeutic effect between two approaches of drug administration. Improvement of positive control group is obvious except a small amount of dander which is probably due to the skin irritation of tretinoin. 4.The concentrations of IL-1、IL-6 and TNF-αof model group are obviously higher than that of normal group(p<0.05). Compared with model group, related cytokine concentrations of prevent group and four treatment groups declined apparently(p<0.05),and those of high-dose treatment groups declined more than those of low-dose treatment groups(p<0.05).Related cytokine concentrations of positive control groups are lower than those of low-dose treatment groups but with no statistical significance(p>0.05), and higher than those of high-dose treatment groups with statistical significance(p<0.05).The difference between negative control group and model group shows no statistical significance(p>0.05).There’s no apparent difference on related cytokine concentrations between two approaches of drug administration.5. The concentrations of NE、MMP-1、MMP-2 and Cath-G of model group are obviously higher than that of normal group(p<0.05). Compared with model group, related enzyme concentrations of prevent group and four treatment groups declined apparently(p<0.05),and those of high-dose treatment groups declined more than those of low-dose treatment groups(p<0.05). Related enzyme concentrations of positive control groups are lower than those of low-dose treatment groups and higher than those of high-dose treatment groups with statistical significance(p<0.05). The difference between negative control group and model group shows no statistical significance( p > 0.05).There’s no apparent difference on related enzyme concentrations between two approaches of drug administration.Conclusions 1. Guinea pig photoaging model was successfully established through 0.1% 8-MOP combined with UVA and UVB exposure add up to 120 hours. 2. Photoaging process could be prevented by AAT. 3. The therapeutic effect of AAT on photoaging is better than tretinoin. 4. The therapeutic effect of AAT on photoaging is dose-dependent. 5. AAT could be absorbed by intraperitoneal injection and external use. 6.One of the probable mechanism for AAT preventing and treating photoaging is inhibiting generating of related inflammatory cytokines, such as IL-1、IL-6 and TNF-α. 7. One of the probable mechanism for AAT preventing and treating photoaging is inhibiting generating of related enzymes, such as NE、MMP-1、MMP-2 and Cath-G.