Compounds for the treatment of ischemia-reperfusion injury
A compound and drug technology, applied in the field of compounds for the treatment of ischemia-reperfusion injury, can solve the problems of injury and high mortality in patients with acute myocardial infarction
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Embodiment 1
[0146] Example 1 The inhibitory effect of ML355 on liver ischemia-reperfusion injury is dose-dependent
[0147] In order to verify the inhibitory effect of different doses of ML355 on hepatic ischemia-reperfusion injury, C57 mice were randomly divided into 4 groups and injected with 1 mg / kg ML355 (HY-12341, MCE Company), 2 mg / kg ML355, and 3 mg / kg via the tail vein respectively. kg ML355 and solvent (control group, DMSO:Solutol:PEG400:water=5:10:20:65(v:v:v:v)), and then perform I / R surgery according to the method of the aforementioned liver I / R animal model . At different time points after operation, serum and liver tissue were collected for detection of ALT and AST enzyme activity and HE staining.
[0148] The test results of ALT and AST are as follows: Figure 1A , Figure 1B As shown, compared with the solvent control group, after ML355 administration, the contents of ALT and AST in the mouse serum were significantly reduced at 6 hours after operation, and the contents o...
Embodiment 2
[0150] Example 2 ML355 effectively alleviates liver function damage caused by ischemia-reperfusion
[0151] To study the protective effect of ML355 on liver ischemia-reperfusion at different time, C57 mice were randomly divided into 7 groups, 20 in each group. Ten mice in each group were given 3 mg / kg of ML355 dissolved in solvent by tail vein injection, and the other 10 mice were given solvent. After the administration was completed, 7 groups of mice were subjected to I / R surgery (one group was the Sham control group, and the remaining 6 groups were the I / R experimental group), and the Sham control group and postoperative 0h, 1h, 3h, 6h, 12h, 24h I / R experimental group mouse serum, ALT, AST detection, to evaluate the degree of liver function damage; Sham control group and postoperative 0h, 6h I / R experimental group mouse liver tissue, made paraffin sections, TUNEL Staining, Mac1 immunofluorescence staining and Ly6G immunofluorescence staining were used to evaluate the apopto...
Embodiment 3
[0156] Example 3 Inhibition of ML355 on ischemia-reperfusion injury in different tissues
[0157] 1. ML355 inhibits cardiac ischemia-reperfusion injury
[0158] C57 mice were randomly divided into 4 groups (Sham group, I / R 6h group, I / R 12h group, I / R 24h group), 7 mice in the Sham group, and 15 mice in each of the other 3 groups. Seven mice were given 3 mg / kg of ML355 dissolved in solvent by tail vein injection, and the other 8 mice and the Sham group were given solvent. After administration, I / R surgery was performed on the mice in the 4 groups, and the serum of mice in the Sham control group and the I / R experimental group at 6h, 12h, and 24h after operation were collected for CK and LDH detection to evaluate the degree of heart damage.
[0159] Experimental results such as Figure 6A and 6B As shown, the content of CK and LDH in serum increased significantly after I / R. After ML355 was administered through the tail vein, the CK content in serum at each time point after I...
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