OBJECTIVE: To investigate the protective effects and mechanisms of camel whey protein (CWP) against myocardial injury in mice with sepsis caused by Gram-positive bacteria or Gram-negative bacteria. METHODS: Using a random number table, 40 male C57BL/6 mice were divided into the Sham group, Gram-positive bacterial sepsis group (G+ group), CWP-pretreated Gram-positive bacterial sepsis group (G+CWP group), Gram-negative bacterial sepsis group (G- group), CWP-pretreated Gram-negative bacterial sepsis group (G-CWP group), with 8 mice in each group. The Gram-positive bacterial sepsis model and the Gram-negative bacterial sepsis model were established by intraperitoneal injection of 1 mL of Staphylococcus aureus/Escherichia coli suspension, respectively; the Sham group received an equal volume of saline. In the pretreatment groups, CWP (200 mg/kg, 250 μL) was administered via oral gavage once daily for 7 days prior to model induction; the remaining groups received an equal volume of saline via oral gavage. Seven days after modeling, echocardiography was used to assess cardiac function parameters, including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV). The levels of serum myocardial injury markers [MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI)] and inflammatory factors [interleukins (IL-1β, IL-6, IL-10), tumor necrosis factor-α (TNF-α)] were measured by enzyme linked immunosorbent assay (ELISA). Pathological changes in myocardial tissue were observed by hematoxylin-eosin (HE) staining. The expression of proteins associated with the PI3K/AKT/NF-ΚB signaling pathway in myocardial tissue were detected by Western blotting. RESULTS: Compared with the Sham group, the G+ and G- groups showed decreased cardiac function parameters (LVEF and LVFS) and increased LVEDD, LVESD, LVEDV, and LVESV, as well as elevated serum levels of CK-MB, cTnI, TNF-α, IL-1β, IL-6, and IL-10; myocardial tissue showed widened interfiber spaces, marked interstitial congestion, inflammatory cell infiltration, and increased myocardial injury pathological scores; the expression of phosphorylated PI3K (p-PI3K), phosphorylated AKT (p-AKT), and phosphorylated P65 (p-P65) proteins were upregulated in myocardial tissue (all P<0.05). Compared with the corresponding G+ and G- groups, the G+CWP and G-CWP groups showed improvements in cardiac function, with increased LVEF and LVFS [LVEF: 0.582±0.033 vs. 0.464±0.019, 0.636±0.040 vs. 0.561±0.027; LVFS: (29.66±1.92)% vs. (22.11±1.67)%, (33.13±2.80)% vs. (27.69±1.93)%], while LVEDD, LVESD, LVEDV, and LVESV decreased [LVEDD (mm): 2.64±0.13 vs. 3.38±0.29, 2.58±0.19 vs. 2.98±0.27; LVESD (mm): 1.65±0.09 vs. 2.42±0.24, 1.70±0.12 vs. 2.45±0.21; LVEDV (μL): 43.67±8.93 vs. 70.08±3.31, 35.40±2.94 vs. 47.73±4.86; LVESV (μL): 19.73±4.79 vs. 36.36±2.89, 14.16±2.54 vs. 21.90±3.49]; reduced serum levels of cTnI, CK-MB, IL-1β, IL-6, and TNF-α [cTnI (ng/L): 855.37±15.22 vs. 1 415.93±14.85, 727.42±18.55 vs. 1 089.57±15.11; CK-MB (μg/L): 14.13±1.30 vs. 20.63±1.52, 8.75±1.48 vs. 17.81±0.88; IL-1β (ng/L): 252.79±18.77 vs. 398.89±11.23, 242.09±13.49 vs. 363.45±8.78; IL-6 (ng/L): 142.93±5.78 vs. 205.15±2.74, 104.18±7.16 vs. 173.29±5.60; TNF-α (ng/L): 181.33±4.47 vs. 271.44±7.43, 134.97±10.49 vs. 241.20±6.86], levels of the anti-inflammatory factor IL-10 increased (ng/L: 248.22±11.71 vs. 205.57±13.69, 312.90±8.82 vs. 256.52±8.12); pathological damage to myocardial tissue was reduced, with lower scores (0.83±0.20 vs. 1.71±0.12, 0.73±0.08 vs. 1.74±0.13); the expression of p-PI3K, p-AKT, and p-P65 proteins were all reduced in myocardial tissue [p-PI3K/β-actin: 0.49±0.20 vs. 0.93±0.08, 0.53±0.02 vs. 0.67±0.05; p-AKT/β-actin: 0.75±0.17 vs. 1.10±0.12, 0.73±0.10 vs. 0.92±0.05; p-P65/β-actin: 0.38±0.04 vs. 0.59±0.09, 0.39±0.07 vs. 0.54±0.03], with all differences being statistically significant (all P<0.05). CONCLUSIONS: CWP can suppress the excessive release of pro-inflammatory cytokines in the serum of mice with sepsis caused by Gram-positive bacteria or Gram-negative bacteria, promote the upregulation of anti-inflammatory cytokines, alleviate inflammatory responses in the myocardial tissue of septic mice, and improve their cardiac function; its mechanism may be related to the regulation of the PI3K/AKT/NF-ΚB signaling pathway.