OBJECTIVETo investigate the feasibility of strategy of allograft tolerance induction by injection of FasL-decorated donor splenocytes.

METHODSChimeric FasL with core streptavidin (SA-FasL) was efficiently displayed on the surface of splenocytes by the technology of ProtEx™. Heterotopic heart transplant procedures were performed from donor WF rats to recipient ACI rats, F344 rats were used as third-party. Intraperitoneal injection of ACI rats with "decorated" WF splenocytes was used as the approach to induce tolerance in this study. According to different therapeutic strategies, three groups were set up: SA-FasL group (n = 23), SA group (n = 20) and naive splenocytes only group (n = 8). No treatment group was regarded as control (n = 10). Adoptive transfer was underwent with injection of splenocytes from tolerant recipients into naive ACI followed by heart transplant procedures. Mixed lymphocyte reaction (MLR) and third party transplantation were performed to detect allogenic tolerance.

RESULTSThe injection of ACI rats with WF rat splenocytes displaying SA-FasL on their surface resulted in tolerance to donor, but not F344 third-party cardiac allografts. There were 70% cardiac allografts in SA-FasL group achieved long term survival, and it was significantly higher than the rats in other groups (P < 0.05). Adoptive transfer of splenocytes from long-term graft recipients into naive unmanipulated ACI rats resulted in indefinite survival of secondary WF grafts. Donor specific tolerance was identified by MLR and third-party transplant.

CONCLUSIONThe direct display of SA-FasL on the cell membrane in a rapid and efficient manner provides a practical and clinically applicable means of immunomodulation for tolerance induction with considerable therapeutic potential for transplantation.

Animals ; Fas Ligand Protein ; genetics ; immunology ; Heart Transplantation ; immunology ; Male ; Rats ; Rats, Inbred ACI ; Rats, Inbred F344 ; Rats, Inbred WF ; Spleen ; cytology ; metabolism ; Tissue Donors ; Transplantation Tolerance ; immunology

To establish a murine carotid artery transplantation model for the study of the chronic rejection, 80 rats were divided into two groups, an allotransplant (ACI-Lewis) group and an isotransplant (Lewis-Lewis) group (control group). The donor carotid artery and the recipient carotid artery were anastomosed by using a polyethylene cuff (internal diameter: 0.7 mm, length: 3 mm).The pathological changes of carotid artery transplant were observed 14, 28 and 56 days after the transplantation. The results showed that the model was successfully established in 95% of the animals. The chronic rejection-associated arteriosclerosis was induced 28 days after the transplantation. The new chronic rejection model of carotid artery by using cuff technique caused fewer traumas and was easy to make. The pathological changes of the transplant mimicked the chronic rejection-associated arteriosclerosis found in human transplant.
Anastomosis, Surgical/methods ; Arteriosclerosis ; Carotid Artery, Common/*transplantation ; Delayed Graft Function ; Graft Rejection/*pathology ; Models, Animal ; Polyethylene ; Rats, Inbred ACI ; Rats, Inbred Lew

OBJECTIVETo study the inhibitory effect of Juhua Jueming powder (JJP) on high-risk corneal transplantation immune rejection in rats.

METHODSThe high-risk corneal transplantation immune rejection rat model was established by inducing corneal neoangiogenesis by suture method and the penetrating transplantation. Model rats were divided into two groups, the treated group and the control group, they were administered with JJP 0.1 g (dissolved in 2 mL water) and normal saline respectively via gastric infusion every day after transplantation. The survival status of the allograft, histopathology, local and systemic immune status in the recipients were observed using immunofluorescence histochemistry and flow cytometry.

RESULTSThe survival time of the allograft in the treated group (14.50 +/- 3.55 days) was significantly longer than that in the control group (8.25 +/- 0.71 days, P < 0.01). Levels of Fas, FasL expressions in iris were stronger, and the percentage of CD4 CD FOXP3 positive cells in peripheral blood was less (5.11 +/- 3. 92% vs. 14.81 +/- 2.58%) in the control group than those in the treated group respectively. The concentration of IL-2 was lower while that of IL-10 was higher in aqueous humor of the treated group than those of the control group, respectively.

CONCLUSIONJJP has certain effect for preventing high-risk corneal transplantation immune rejection in rat model.

Animals ; Corneal Transplantation ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Graft Rejection ; prevention & control ; Phytotherapy ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew

*Chemoembolization, Therapeutic ; Liver Neoplasms, Experimental/*therapy ; Microspheres ; Polyglactin 910/*therapeutic use ; Rats, Inbred ACI

BackgroundThe effectiveness of the combination of electroacupuncture (EA) and behavioral training (BT) for mid/advanced cerebral infarction (M/ACI) and related mechanisms remains unclear. This study aimed to investigate the combined effects on the learning-memory ability and event-related potential P300 in rats with M/ACI.

MethodsEighty rats with M/ACI were divided into Group Model (M), Group EA, Group BT, and Group EA-BT (n = 20) according to the random number with five healthy rats in Group Control (CON). On the 6 week after modeling, EA, BT, and EA-BT were given to Group EA, Group BT, and Group EA-BT, respectively, whereas Group M and Group CON were not given any intervention. Y-maze test and P300 were recorded before and after the intervention.

ResultsAfter intervention, the P300 latency was lower and the amplitude was higher in the Group EA-BT, Group EA, and Group BT than before (for latency, t = -7.638, -4.334, and -5.916; for amplitude, t = 8.125, 3.846, and 5.238; P < 0.01), with Group EA-BT superior to Group EA (for latency, t = -3.708; for amplitude, t = 3.653; P < 0.01) and Group BT (for latency, t = -2.067; for amplitude, t = 2.816; P < 0.05), with no significant difference between Group BT and EA (for latency, t = -1.439; for amplitude, t = 1.075; P > 0.05). While the performances of Y-maze tests in the Group EA-BT, Group EA, and Group BT were all better than before (t = 10.359, 4.520, and 7.791, P < 0.01), with Group EA-BT better than Group EA (t = 5.627, P < 0.01) and Group BT (t = 2.913, P < 0.01) respectively, and Group BT better than Group EA (t = 2.912, P < 0.01).

ConclusionEA or BT can affect P300 in rats with M/ACI, and the combination of these two methods can significantly improve the learning-memory ability.

Acupuncture Points ; Animals ; Cerebral Infarction ; Disease Models, Animal ; Electroacupuncture ; Evoked Potentials ; Humans ; Rats ; Rats, Inbred ACI ; Rats, Sprague-Dawley

Animals ; Chemoembolization, Therapeutic ; Liver Neoplasms, Experimental ; therapy ; Male ; Microspheres ; Polyglactin 910 ; therapeutic use ; Rats ; Rats, Inbred ACI

OBJECTIVETo evaluate the effect of HSGJ on chronic allograft nephropathy (CAN) using standard rat model of CAN.

METHODRenal transplantation was performed with Fisher rats as donors and Lewis rats as recipients. All the recipients were randomly divided into control group and medication groups (high and low dosage of HSGJ, fed every other day). After 16 weeks of treatment, renal function and the histological alteration of CAN were measured. The expression of the TGFbeta1 mRNA in the allograft was evaluated by real-time PCR.

RESULTThe content of 24 h urine protein and the level of serum creatinine in the medication groups were significantly decreased (P < 0.01) as compared with control group, whereas the creatinine clearance was increased (P < 0.01). The degree of glomerular sclerosis and the Banff score of medication groups were lower than the control group respectively (P < 0.01), in consistent with decreased expression of the TGF 1mRNA.

CONCLUSIONHSGJ can prevent the chronic allograft nephropathy and the mechanism may be related with its influence on the expression of the TGFbeta1.

Animals ; Chronic Disease ; Drugs, Chinese Herbal ; therapeutic use ; Glomerulonephritis ; etiology ; immunology ; prevention & control ; Graft Rejection ; drug therapy ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; adverse effects ; Random Allocation ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Transplantation, Homologous

An orthotopic penetrating keratoplasty model was developed in the rat. An oversized (0.5 mm) graft was used and 8 interrupted sutures were applied. These sutures were not removed. Eleven grafts out of 13 were rejected by the 3rd week in the disparate group (Brown Norway rat to Lewis rat transplantation group), which was characterized by edema, opacity, and neovascularization. All grafts remained clear in the syngeneic group (Lewis rat to Lewis rat transplantation group). Immunohistochemical examination was performed. This model seems to be a reliable and reproducible one to evaluate rejection reaction in corneal transplantation.
Animals ; Female ; Graft Rejection ; Keratoplasty, Penetrating/immunology/*methods/pathology ; Lymphocyte Subsets/immunology/pathology ; Macrophages/immunology/pathology ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Transplantation, Homologous ; Transplantation, Isogeneic

OBJECTIVETo investigate the mechanism underlying the inhibitory effect of tacrolimus (FK506) against acute liver graft rejection.

METHODSRat models of orthotopic liver transplantation were divided into 3 groups, namely the tolerance group with Brown Norway (BN) rats as the donors and Lewis rats as the recipients, rejection group with Lewis rats as donors and BN rats as recipients, and FK506 group with the same donor-recipient pair as in the rejection group and FK506 treatment. The recipients were sacrificed 7 days after the transplantation, and the hepatic histology, cytokine levels, and glucocorticoid-induced tumor necrosis factor-related protein ligand (GITRL) expression in the liver and Kupffer cells were observed and detected.

RESULTSCompared with the tolerance group, the rejection group showed increased GITRL expressions in the liver and Kupffer cells (P<0.05), which was significantly lowered by FK506 treatment (P<0.05). Acute liver graft rejection caused significantly elevated interferon-γ (IFN-γ) levels and decreased interleukin-10 (IL-10) levels in the plasma and Kupffer cells (P<0.05), and these changes were obviously attenuated by FK506 treatment (P<0.05).

CONCLUSIONThe effect of FK506 in suppressing acute liver graft rejection is probably associated with down-regulated GITRL expression in the liver and Kupffer cells.

Animals ; Carrier Proteins ; metabolism ; Graft Rejection ; prevention & control ; Kupffer Cells ; metabolism ; Liver ; metabolism ; Liver Transplantation ; Male ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Tacrolimus ; pharmacology

To investigate the gene expression profiles in acute allograft rejection of renal transplantation, and identify the markers for the early diagnosis of acute rejection, heterotopic kidney transplantation was performed by using F344 or Lewis donors and Lewis recipients. No immunosuppressant was used. Renal grafts were harvested on days 3, 7, and 14. A commercial microarray was used to measure gene expression levels in day-7 grafts. The expression levels of 48 genes were up-regulated in the allograft in comparison with the isograft control, and interferon-gamma-induced GTPase gene was most significantly up-regulated in allografts. It is concluded that a variety of pathways are involved in organ transplant rejection which is dynamic and non-balanced. IFN-inducible genes, such as IGTP, may play an important role in the rejection. A lot of important factors involved in acute rejection are unnecessary but sufficient conditions for the rejection. We are led to conclude that it is virtually impossible to make an early diagnosis based on a single gene marker, but it could be achieved on the basis of a set of markers.
Gene Expression Profiling ; Gene Expression Regulation ; Graft Rejection/*genetics ; Graft Rejection/metabolism ; Kidney/*metabolism ; Kidney Transplantation ; MAP Kinase Signaling System ; Oligonucleotide Array Sequence Analysis ; Rats, Inbred F344 ; Rats, Inbred Lew ; Signal Transduction ; Species Specificity ; Time Factors ; Transplantation, Homologous