Intervention with Schistosoma japonicum cysteine protease inhibitor for treatment of lipopolysaccharide-induced sepsis in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of Schistosoma japonicum cysteine protease inhibitor (rSjCystatin) for treatment of lipopolysaccharide (LPS)-induced sepsis in mice.</p><p><b>METHODS</b>After a week of adaptive feeding, 54 BALB/c mice were randomly divided into normal control group (group A), sepsis group (group B), and rSjCystatin intervention group (group C). The mice in group A received an intraperitoneal injection of PBS (100 µL), and those in groups B and C were injected with PBS (100 µL) containing LPS (10 mg/kg); the mice in group C were also intraperitoneally injected with 25 µg sjCystatin in 100 µL PBS 30 min after LPS injection. From each group, 10 mice were randomly selected 24 h after PBS or LPS injection for detecting serum levels of TNF-α, IL-6, and IL-10 using ELISA and the levels of ALT, AST, BUN, and Cr using automatic biochemical analyzer; the pathological changes in the liver, lung and kidney were observed with HE staining. The remaining 8 mice in each group were used for observing the changes in the general condition and the 72-h survival.</p><p><b>RESULTS</b>The 72-h survival rates of the mice was 100% in group A, 0 in group B, and 36% in group C, showing a significant difference among the 3 groups (P<0.05). Compared with those in group A, the mice in group B exhibited obvious liver, lung, and renal pathologies with increased levels of ALT, AST, BUN, Cr, IL-6, and TNF-α (P<0.05). Treatment with sjCystatin significantly lessened LPS-induced organ pathologies, lowered the levels of liver and renal functional indexes and the pro-inflammatory cytokines, and increased the serum level of IL-10 in the mice (P<0.05).</p><p><b>CONCLUSION</b>SjCystatin can produce a significant therapeutic effect on sepsis induced by LPS in mice.</p>

[Effect of excretory/secretory protein of Trichinella spiralis adult worm on CLP-induced sepsis in mice].

OBJECTIVE: To observe the effect of excretory/secretory products from Trichinella spiralis adult worms (AES) on cecal ligation and puncture (CLP) -induced sepsis in mice. METHODS: Forty-eight BALB/c mice were randomly divided into 3 groups：a sham operation group (PBS + sham group, Group A), a CLP-induced sepsis group (PBS+CLP group, Group B) and an AES treatment group (AES+CLP group, Group C). The mice of each group were intraperitoneally injected with 25 µg of AES or PBS only as a control in a total volume of 200 µl. Eight mice from each group were selected randomly for survival analysis of 96 hours. The other 8 mice in each group were observed for pathological changes in the lung, liver and kidney tissues by HE staining 12 h after CLP, and then determined for the detection of cytokines including TNF-α, IL-1ß, IL-6, IL-10 and TGF-ß in the sera by ELISA. RESULTS: The difference among the survival rates of mice in the 3 groups was statistically significant (χ2 = 21.16, P < 0.05). Compared to Group A (100%), the survival rate of mice in Group B (0) decreased significantly (P < 0.05), and also the pathological damage degrees in the lung, liver and kidney tissues of the mice in Group B increased significantly after CLP. Compared with the mice in group B, the survival rate of those in Group C (70%) increased significantly (P < 0.05), and the pathological damage degrees in the lung, liver and kidney tissues of the mice in Group C decreased significantly after the treatment with AES. The differences among the levels of pro-inflammatory cytokines TNF-α (F = 27.11, P < 0.05), IL1ß (F = 18.75, P < 0.05) and IL-6 (F = 100.93, P < 0.05) in the sera of the mice in the three groups were statistically significant. Compared with the mice in Group A, the levels of the 3 cytokines of those in Group B increased significantly (all P < 0.05). However, after the treatment with AES, the levels of the pro-inflammatory cytokines of those in Group C decreased significantly (all P < 0.05). The differences among the levels of immunoregulatory cytokines IL-10 (F = 10.88, P < 0.05) and TGF-ß (F = 11.37, P < 0.05) in the sera of the mice in the three groups were also statistically significant. Compared with the mice in Group B, the levels of IL-10 and TGF-ß of those in Group C were higher after treatment with AES (both P < 0.05). CONCLUSIONS: T. spiralis AES has a therapeutic potential for alleviating sepsis induced by CLP in mice.

Effect of Trichinella spiralis and its worm-derived proteins on CLP-induced sepsis in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of Trichinella spiralis and its worm-derived proteins on cecal ligation and puncture (CLP)-induced sepsis in mice.</p><p><b>METHODS</b>Eighty male BALB/c mice were randomly divided into sham-operated group, CLP group, Trichinella spiralis muscle larvae (ML) pre-infection group (ML+CLP group), soluble muscle larvae proteins (SMP) treatment group (SMP+CLP group) and excretory-secretory proteins (MES) treatment group (MES+CLP group). In ML+CLP group, the mice were orally infected with 300 Trichinella spiralis muscle larvae at 28 days before CLP and those in the other groups were intraperitioneally injected with PBS or SMP (25 µg/mice) or MES (25µg/mice) 30 min after CLP. The general condition and 72-h survival after CLP of the mice were observed. The levels of alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), creatinine (Cr), TNF-α, IL-6, IL-1β, IL-10 and TGF-β were measured at 12 h after the operation, and the pathological changes of the liver and kidney were observed.</p><p><b>RESULTS</b>s Compared with the sham-operated mice, the mice in CLP group showed decreased 72-h survival, obviously increased ALT, AST, BUN, Cr, TNF-α, IL-6, IL-1β, IL-10, and TGF-β with hepatic cords disorder, hepatocytes swelling, glomerulus shrinkage, and renal tubular cell edema. Compared with CLP group, the mice in ML+CLP group showed lowered levels of ALT, AST, Cr, TNF-α and IL-1β and increased levels of IL-10 and TGF-β; in SMP+CLP group, the levels of ALT, AST, Cr, TNF-α and IL-1β were decreased and TGF-β increased. In MES+CLP group, the mice showed obviously increased 72-h survival with lowered levels of ALT, AST, BUN, Cr, TNF-α, IL-6 and IL-1β, increased levels of IL-10 and TGF-β, and alleviated liver and kidney damages.</p><p><b>CONCLUSION</b>Trichinella spiralis and its worm-derived proteins can decrease the levels of pro-inflammatory cytokines and increase immunomodulatory cytokines, and MES has more potent effect to reduce structural and functional damages of the liver and kidney.</p>