| Corneal transplantation is the most successful form of the organ allograft, and also is the most important operation to regain the eyesight. The previous studies show that the rejection rate in the so-called low-risk cases is only 10%, yet as in the high-risk cases is higher than 65%. Those high-risk factors are including vascularized cornea, prolonged inflammation, severe chemical injury of the cornea and conjunctiva, large size keratoplasty, and re-keratoplasty. The rejection free survival can not be highly raised by matched HLA, or by systemic or topical administration of the immunosuppressive therapy. Nowadays, it's an urgent problem that how to raise the survival rate of the high-risk keratoplasty.Tripterygium wilfordii hook.f. is one of Chinese herbs, which has the effect of immunosuppression, antiinflammation, anti-procreation, anti-neoplasm, and antiseptic. But because of its side-effect to the hematopoietic system, heart, liver, kidney, and genital system by systemic administration, it can not be widely used in the clinic.In this research we intend to make the new topical ophthalmic solution of tripterygiitotorum (Tn) from this herb, apply on the keratoplasty, and study the effect of this new type herb on preventing the rejection in the rat model and in clinic. We also study on the regimens of this herd combined with the administration of anti-neovascularized ophthalmic solutions and other immunosuppressive therapy, inorder to lower the rejection rate in clinic or prolong the survival of the graft in the experiment at perforating keratoplasty. We also study on the role of limbal stem cell in the rejection by mixed lymphocyte culture.I. Studies on Pharmacokinetics of Tripterygiitotorum and TriptolideOphthalmic SolutionObjectiveTo observe the pharmacokinetic data of the tripterygiitotorum (Tn) and triptolide (Tio) ophthalmic solution in the eye by high performance liquid chromatography (HPLC).MethodsAqueous humor levels of triptolide following administated 50ul topical 0.03% TH eye-drops or 50 u 1 topical 1.0 u g/ml TIO eye-drops were measured at intervals within 4 hours by HPLC.ResultsThose two ophthalmic solutions in the aqueous humor concentration-time data was shown to be subjected to one-compartment model. As for TH, the concentration aqueous humor-time average equation of rabbit eyes was C(t)= 178.123 X Dose XKa=2.708h-1; Lagtime=0.456h; t1/2(ka)=0.256h; t1/2(ke)=0.339h; T(max)=0.880h; C(max)=0.278ug/ml;AUC=0.323 ug h ml-1.As for the T10 eye-drops, the concentration aqueous humor-time average equation of rabbit eyes was C(t)=44.62 X Dose X the important parameters: A=2.23 u g/ml; Ke=2.01h-1; Ka-2.80 h-1; Lag time=0.43h; t,/2(ka)=0.25h; t,/2(ke)=0.34h; T(max)=0.85h; C(max)=0.27u g/ml; AUO0.31 u g h ml-1.ConclusionThe peak concentration of the TH or T10 ophthalmic solution in the anterior chamber appeared in 0.88 hours after it was applied, and vanished in 4 hours.II Study on the Stimulation and Toxicity of the Tripterygiitotorum Ophthalmic Solution in vivo and ex vivoObjectiveTo determine the safe concentration of the tripterygiitotorum ophthalmic solution for topical use.MethodsDifferent concentrations of uipterygiitotorum ophthalmic solutions were topically used in the 10 eyes of Wistar rats and New Zealand white rabbits. We evaluated the eye stimulation and toxicity of each concentration by the standard of reaction to stimulated eye, and stained the cornea by fluorescein sodium. At last, we did the HE stain; the results were all compared with the normal one. The investigator as the normal human used the eye-drops to feel the stimulation and researched the cornea toxicity by fluorescein sodium stain. The toxicity of different concentrations to the extent of dead rabbits' corneal epithelial cells was measured by 0.4% Trypan Blue stain in vitro.ResultsThe marks of the eye stimulated reaction by topical using the concentration of 200ug/ml 300ug/ml TU and the control groups are 1-3, the 450ug/ml TH is...
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