Aim To study the pharmacokinetics of po-lyethylene glycol conjugation on EILDVP peptide in mice by injection through tail vein.Methods KM mice,saturated thyroid gland with compound of NaI, were injected for 1 25 I labeled EILDVP-Tyr-NH2 ,EILD-VP-Cys (mPEG2000-MAL)-Tyr-NH2 and EILDVP-Cys (mPEG20000-MAL)-Tyr-NH2 peptides (1 25 I:5 mL · kg -1 volume 3.441 GBq·L -1 concentration)by tail intravenous,respectively.Blood samples at different time intervals were obtained,blood plasma was separa-ted,and the radioactivity of precipitation after trichloro-acetic acid (TCA)treatment was tested.According to standard curve equation, the plasma concentration curve and pharmocokinetic parameters were depicted by means of 3P97 pharmocokinetics software.Results Concentration range of 3.75 ~480 μg·L -1 of three 1 25 I labled peptides in plasma from mice had good line-ar relationship.Recovery of method was 88.92% ~
1 06.66%,and RSD <1 0%.The half-life time (T1 /2 ) of EILDVP-Tyr-NH2 peptide modified by mPEG2000 and mPEG20000 ,labled by 1 25 I was 0.43h and 1 .94h,re-spectively,which was 1 .54 times and 6.93 times that of prototype peptide (T1 /2 =0.28h),and the clear-ances (Cl)were 1 .23 times and 24.71 times,respec-tively.The apparent distribution volume (V)values of the three species were small,which might mainly dis-tributed in the plasma.Conclusions Suitable for mo-lecular mass mPEG modified the EILDVP peptides could extend to maintain time in vivo,which could play a positive role in improving efficacy.In the experimen-tal range,EILDVP peptide modified by larger molecu-lar mass of mPEG20000 has better effect.

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep