Construction Of Tree Shrew Infection Model Of Herpes Simplex Keratitis And The Pharmacodynamic Of 14- Decarboxylase-11,12-Two Dehydrogenation Andrographolide Potassium And Sodium Salts Of Succinic Acid Half Ester In The Model

Herpes simplex virus keratitis (herpes simplex keratitis, HSK) is a global keratitis disease of high incidence, blindness rate. It is hard to treat even with a long treatment cycle and easily recurs, making people great suffer in the work and live. In recent years the incidence rate of HSK is still rising. Tree shrew is the closest animal to primates, whose corneal structure is approximately 98% similar to that of human. This makes it an ideal animal for keratitis model.In this work, two types of herpes simplex virus keratitis (HSK) model were built using HSV-117+ and HSV-1 Mckrea respectively. Compared with HSV-117+, the HSV-1 Mckrea keratitis model was more desirable, which had advantages of lower mortality and no scratches needed for infection.We evaluate the therapeutic effects of 14-decarboxylase-11,12-two dehydrogenation andrographolide potassium and sodium salts of succinic acid half ester on the HSV-1 Mckrea models. The high (125 mg/ml) and medium (62.5 mg/ml) concentrations of 14-decarboxylase-11,12-two dehydrogenation andrographolide potassium and sodium salts of succinic acid half ester achieved good therapeutic effects on the 14th day of treatment, even better than the acyclovir positive control. The low concentration (31.25 mg/ml) also had certain therapeutic effect, but not as significant as that of the high and medium concentrations.The replication of the HSV-1 in the cornea of tree shrew was analysied by qPCR.14-decarboxylase-11,12-two dehydrogenation andrographolide potassium and sodium salts of succinic acid half ester and Acyclovir both inhibited the replication of the HSV-1 in vivo, and the inhibitory rate of Acyclovir was slightly higher than that of the Andrographolide groups.14-decarboxylase-11,12- two dehydrogenation andrographolide potassium and sodium salts of succinic acid half ester inhibited the the virus in a concentration-dependent manner. The results of qPCR of the inflammatory cytokines indicated that 14 decarboxylase-11,12-two dehydrogenation andrographolide potassium and sodium salts of succinic acid half ester and acyclovir could either inhibit gene expression of proinflammatory factor beta IL-1 and IL-6, or promote the gene expression of IFN-γ to achieve the anti-inflammatory effect.