Objective: To explore the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] on lymphocytes apoptosis and the expression of Toll-like receptors (TLR) 4 and 9 in rats with severe acute pancreatitis (SAP). Methods: 90 rats were randomly divided into 5 groups with 15 rats in each: normal control group (A), model control group (B), low-dose group (C), medium-dose group (D), high-dose group (E) and positive drug control group (F). Except for group A, the rats were made into SAP models with sodium taurocholate in the other groups. Groups C, D and E were intraperitoneally injected with2.5, 5 and 10 μg·kg-1 1, 25(OH)2 D3, respectively. The group F was subcutaneously injected with 40 mg·kg-1 octreotide. The pathological damage in pancreatic tissues was observed by HE staining. The content of Caspase 3 in pancreatic tissues was detected by immunohistochemistry. The mRNA and proteins expression of Caspase 3 and Caspase 9 were detected by real-time fluorescent quantitative PCR and Western blot. The levels of inducible nitric oxide synthase (iNOS), interleukins (IL-6, IL-4, IL-10) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay and RT-PCR. The expression of TLR4 and TLR9, and phosphorylation of nuclear factor κB (NF-κB) in pancreatic tissues were detected by Western blot. Results: Compared with group A, the number of Caspase 3 positive cells, the relative levels of Caspase 9 and Caspase 3 mRNA, the values of cleaved Cas9/Cas9 and cleaved Cas3/Cas3, the expression of iNOS, IL-6, IL-4, IL-10 and TNF-α, the relative expression of TLR4 and TLR9 proteins, and phosphorylation level of p65 were significantly increased in group B (P<0.05). Compared with group B, the number of caspase-3 positive cells, the relative levels of Caspase 9 and Caspase 3 mRNA, the values of cleaved Cas9/Cas9 and cleaved Cas3/Cas3, the expression of iNOS, IL-6 and TNF-α, the relative expression of TLR4 and TLR9 proteins, and the phosphorylation level of p65 were significantly decreased in groups D, E and F, while the expressions of IL-4 and IL-10 were significantly increased (P<0.05). Conclusion: 1,25(OH)2 D3 can inhibit lymphocytes apoptosis and alleviate inflammatory response in SAP rats, which may be related to inhibiting the expression of TLR4 and TLR9.
WU Hai-tao, SHI Hai-xia, SONG Yu, ZHOU Hong-li
. Effects of 1,25-dihydroxyvitamin D3 on lymphocytes apoptosis and the expression of Toll-like receptors 4 and 9 in rats with severe acute pancreatitis*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(12)
: 2063
-2069
.
DOI: 10.16155/j.0254-1793.2021.12.03
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