Abstract:Objective:To observe the effect of Celastrol (Cel) on hepatorenal cell apoptosis of rats with preeclampsia (PE) and its protective effect. Methods:A total of 50 pregnant SD rats were randomly divided into the control group,the PE group,the PE+low-dose Cel (PE+L-Cel) group,the PE+medium-dose Cel (PE+M-Cel) group and the PE+high-dose Cel (PE+H-Cel) group,with 10 rats in each group. PE rat model was induced by injection of lipopolysaccharide through tail vein,and rats in the PE+L-Cel group,the PE+ M-Cel group and the PE + H- Cel group were respectively given the intraperitoneal injection with 5, 10, and 20 mg/(kg·d) of tretinoin glycosides per day from the day 14 of gestation to the day 20,and equal volumes of 0.9% sodium chloride solution were respectively injected into the Control group and the PE group. After treatment,the systolic pressure (SBP) and urinary albumin of rats in each group were detected respectively. Using terminal- deoxynucleotidyl transferase mediated dUTP nick- end labeling (TUNEL) method, the cell apoptosis in hepatorenal tissue was detected. The expressions of B- cell lymphoma- 2 (Bcl- 2) gene and activated cysteinyl aspartate specific proteinase- 9 (Caspase- 9) antibody in hepatorenal tissues were detected by immunohistochemical staining. The levels of serum interferon- γ (IFN- γ) , interleukin-4 (IL-4),interleukin-17 (IL-17) and interleukin-10 (IL-10) of rats were detected by enzymelinked immunosorbent assay (ELISA) method. The percentage of peripheral blood T helper cell 1 (Th1), T helper cell 2 (Th2), T helper cell 17 (Th17), and regulatory T cell (Treg) of CD4 + was detected by flow cytometry. Results:Comparing with those in the Control group,the levels of SBP and urinary albumin in the PE group were increased (P<0.05),the protein expression levels of VEGF,MMP- 2 and MMP- 9 in placental tissues were decreased (P<0.05), the hepatorenal cell apoptosis rates were increased (P< 0.05), the Caspase- 9 expression levels in hepatorenal tissues were increased (P<0.05), the Bcl- 2 expression levels were decreased (P<0.05), the levels of serum IFN- γ and IL- 17 were increased (P< 0.05),the levels of IL-4 and IL-10 were decreased (P<0.05),the percentage of peripheral blood Th1 and Th17 of CD4+ was increased (P<0.05),and the percentage of Th2 and Treg of CD4+ was decreased (P< 0.05); comparing with those in the PE group, the levels of SBP and urinary albumin in the PE + L- Cel group,the PE+M-Cel group and the PE+H-Cel group were decreased (P<0.05),the protein expression levels of VEGF,MMP- 2 and MMP- 9 in placental tissues were increased (P<0.05),the hepatorenal cell apoptosis rates were decreased (P<0.05),the Caspase- 9 expression levels in hepatorenal tissues were decreased (P<0.05), the Bcl- 2 expression levels were increased (P<0.05), the levels of serum IFN- γ and IL- 17 were decreased (P<0.05), the levels of IL- 4 and IL- 10 were increased (P<0.05), the percentage of peripheral blood Th1 and Th17 of CD4+ was decreased (P<0.05),and the percentage of Th2 and Treg of CD4 + was increased (P<0.05);comparing with those in the PE + L- Cel group,the levels of SBP and urinary albumin in the PE+M-Cel group and the PE+H-Cel group were decreased (P<0.05),the protein expression levels of VEGF, MMP- 2 and MMP- 9 in placental tissues were increased (P<0.05), the hepatorenal cell apoptosis rates were decreased (P<0.05), the Caspase- 9 expression levels in hepatorenal tissues were increased (P<0.05),the Bcl-2 expression levels were decreased (P<0.05),the levels of serum IFN-γ and IL-17 were decreased (P<0.05),the levels of IL-4 and IL-10 were increased (P<0.05), the percentage of peripheral blood Th1 and Th17 of CD4 + was decreased (P<0.05), and the percentage of Th2 and Treg of CD4 + was increased (P<0.05); comparing with those in the PE + M- Cel group, the levels of SBP and urinary albumin in the PE + H- Cel group were decreased (P<0.05), the protein expression levels of VEGF, MMP- 2 and MMP- 9 in placental tissues were increased (P<0.05), the hepatorenal cell apoptosis rates were decreased (P<0.05), the Caspase- 9 expression levels in hepatorenal tissues were increased (P<0.05),the Bcl-2 expression levels were decreased (P<0.05),the levels of serum IFN-γ and IL-17 were decreased (P<0.05),the levels of IL-4 and IL-10 were increased (P<0.05), the percentage of peripheral blood Th1 and Th17 of CD4 + was decreased (P<0.05), and the percentage of Th2 and Treg of CD4+ was increased (P<0.05). Conclusion:Cel can mitigate the symptoms of PE rats and inhibit the hepatorenal cell apoptosis. Cel may exert its therapeutic effect by correcting the imbalance of Th1/Th2 and Th17/Treg in PE rats.