Metabolic dysfunction-associated fatty liver disease is a common chronic liver disease worldwide， and its incidence rate continues to rise. The traditional “two-hit” theory has gradually been replaced by the “multiple-hit” hypothesis， which emphasizes the synergistic effect of multiple pathogenic factors. Necroptosis is an inflammatory form of death with both the morphological characteristics of necrosis and the signaling mechanism of apoptosis， and the core of necroptosis lies in the receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like pseudokinase signaling axis. This pathway directly leads to the death of hepatocytes， and it triggers an inflammatory response and promotes the fibrosis process by releasing damage-associated molecular patterns； the pathway is also closely associated with the metabolic reprogramming of the liver. This review summarizes the activation mechanism of necroptosis in metabolic dysfunction-associated fatty liver disease， analyzes its effect on liver inflammation， fibrosis， and metabolism， and explores its therapeutic strategies and application prospects.

Objective: To clarify that protection of Tongxinluo against myocardial ischemia/reperfusion injury relates to enhancing endothelial barrier in diabetic rats.
Methods: A total of 32 Zucker diabetic rats were randomized into 4 groups:Sham group, Model group, Insulin group and Tongxinluo group, n=8 in each group. In addition, there was a Control group containing 8 non-diabetic Zucker rats. Myocardial ischemia/reperfusion injury model was established by a 45-min ischemia and 3-h reperfusion protocol. The size of infarction was detected by pathological staining, the microvascular permeability was examined by Miles assay to obtain the lfuorescein isothiocyanate concentration in myocardial tissue, the Triton X-100 soluble and insoluble VE-cadherin was measured by membrane protein extraction and western blot analysis.
Results:The size of infarction in Model group was obviously higher than that in Control group (55.2 ± 1.4)%vs (36.2± 1.3)%,P<0.05 and the lfuorescein isothiocyanate concentration was also higher in Model group than Control group. Both insulin group and Tongxinluo group had the similar size of infarction with Model group (36.8 ± 1.2)%vs (38.7 ± 1.1)%, P>0.05. Both insulin group and Tongxinluo group got lower lfuorescein isothiocyanate concentration (all P<0.01) and VE-cadherin internalization (all P<0.05) than that in Model group.
Conclusion: Protection of Tongxinluo against myocardial ischemia/reperfusion injury in diabetic rats is as effective as
insulin, but the effect is independent of reducing blood glucose and may be related to enhancing endothelial barrier.