Objective To evaluate the effect of Iduna protein overexpression on poly(ADP-ribose) polymerase 1 ( PARP-1)∕apoptosis-inducing factor ( AIF) pathway during oxygen-glucose deprivation (OGD)-induced damage to hippocampal neurons in neonatal rats. Methods Primarily cultured hippocam-pal neurons of healthy Sprague-Dawley rats born within 24 h were isolated and cultured. Hippocampal neu-rons were divided into 4 groups (n = 40 each) using a random number table: control group (group C), OGD group ( group O), negative control lentivirus group ( group NL) and Iduna protein overexpression group (group IO). OGD was induced by incubating the neurons in glucose-free medium and hypoxic envi-ronment. Negative control lentivirus and recombinant lentivirus overexpressing Iduna were added at 48 h be-fore establishing the model in NL and IO groups, respectively. Neurons were cultured in the normal culture medium for 24 h in group C. The cell survival rate was detected using methyl thiazolyl tetrazolium assay, the lactic dehydrogenase (LDH) leakage rate was measured using colorimetric method, the comet assay was used to detect DNA content in the tail of neurons, and the expression of PARP-1, cytochrome C (Cyt c) and AIF in the nucleus was detecteded by Western blot. Results Compared with group C, the survival rate of neurons was significantly decreased, the LDH leakage rate and DNA content in the tail of neurons were increased, and the expression of PARP-1, Cyt c and AIF was up-regulated in the other three groups (P<0. 05). Compared with group O, the survival rate of neurons was significantly increased, the LDH leakage rate and the DNA content in the tail of neurons was decreased, and the expression of PARP-1, Cyt c and AIF was down-regulated in group IO (P<0. 05), and no significant change was found in group NL (P>0. 05). Compared with the group NL, the survival rate of neurons was significantly increased, and the LDH leakage rate and DNA content in the tail of neurons were decreased, and the expression of PARP-1, AIF and Cyt c was down-regulated in the group IO (P<0. 05). Conclusion Iduna protein overexpression reduces OGD-induced damage to hippocampal neurons through inhibiting PARP-1∕AIF pathway in neonatal rats.

OBJECTIVE To study the improvement effects of arbutin on myocardial fibrosis （MF） model rats and its mechanism. METHODS The network pharmacology was used to predict the potential target of arbutin in improving MF and molecular docking was used to validated. Totally 50 SD rats were given isoprenaline subcutaneously （5 mg/kg， once a day， for 14 consecutive days） to induce the MF model. Modeled rats were randomly divided into model group， captopril group （9 mg/kg）， arbutin low-dose， medium-dose and high-dose groups （50， 100， 200 mg/kg）， with 10 rats in each group. Another 10 healthy rats were included as normal group. Each group was given the corresponding drugs， once a day， for 28 consecutive days. Twenty-four hours after the final administration， electrocardiograms and heart-related indexes [heart weight index （HWI）， left ventricular weight index （LVWI）] of rats were detected； the levels of creatine kinase （CK）， lactate dehydrogenase （LDH）， N-terminal pro-brain natriuretic peptide （NT-proBNP） and type Ⅰ collagen （Col Ⅰ） and Col Ⅲ were detected in myocardial tissue of rats； the pathological changes of myocardial tissue were observed， and protein and mRNA expressions of adenosine deaminase （ADA） and adenosine kinase （ADK） were detected in the myocardial tissue of rats. RESULTS The results of network pharmacology showed that the main targets of arbutin improving MF were ADA and ADK. The results of molecular docking showed that arbutin bind stably with ADA and ADK. The results of experimental verification showed that compared with model group， the amplitude of ST and T waves in electrocardiogram were improved in administration groups， and the symptoms of atrial flutter were alleviated； HWI （except for arbutin medium-dose group）， LVWI， the levels of CK， LDH， NT-proBNP， Col Ⅰ and Col Ⅲ in the myocardial tissue of rats were decreased significantly （P＜0.05）； the degree of myocardial fibrosis in rats decreased； protein and mRNA expressions of ADA and ADK in the myocardial tissue were significantly increased （P＜0.05）. CONCLUSIONS Arbutin can improve cardiac fibrosis and cardiac function of MF model rats， the mechanism of which may be associated with up-regulating protein and mRNA expressions of ADA and ADK，influencing the nucleotide metabolism and collagen generation. zhangminghao@hactcm.edu.cn

OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 （NLRP3） inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3， apoptosis-associated speck-like protein ， containing a CARD （ASC）， and caspase-1 precursor （pro- No.20-21ZY1053） caspase-1） were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group， model group， dexamethasone group （0.002 g/kg）， and Pangshi antai zhixue decoction low-， medium-， and high-dose groups （11.025， 22.05， 44.10 g/kg）， with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically， once a day， for 12 consecutive days. Except for normal group， other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication， serum levels of triiodothyronine （T3）， thyroxine （T4）， interleukin-2 （IL-2）， IL-4， IL-6， IL-10， and interferon-γ （IFN-γ） were all detected； the abortion rate and uterine coefficient were calculated； the pathological morphology of the pregnant uterus was observed； protein expressions of NLRP3， ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3， ASC， and pro-caspase-1 were all less than －5 kJ/moL. The animal experiment results showed that compared with normal group， the uterine coefficient and serum levels of IL-4， IL-6 and IL-10 were decreased significantly in model group （P＜0.05）； the abortion rate and serum levels of T3， T4， IL-2 and IFN-γ as well as protein expressions of NLRP3， ASC and caspase-1 were increased significantly （P＜0.05）； there were abortion lesions in the pregnant endometrium. Compared with the model group， most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups （P＜0.05）， and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome， down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2， and up-regulating anti-inflammatory cytokines such as IL-4， IL-6 and IL-10， thereby improving spontaneous abortion with heat syndrome.