Aims: Renal fibrosis is a common outcome of chronic kidney disease. This study was designed to examine the protective effects of resveratrol (RSV) against renal fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the potential mechanism involved. Methods: Mice were randomly divided into three groups: sham-operated, UUO, and UUO/RSV (20 mgÁkg À1 Áday À1). Histological changes were examined using periodic acid-Schiff and Masson's trichrome staining after 14 days. Superoxide dismutase (SOD), malondialdehyde (MDA), and 8-OHdG levels were determined using a commercially available kit. ICAM-1, TNF-a, and TGF-b levels were measured using real-time PCR. Fibronectin levels were measured by western blot, and the Smad3 acetylation and Sirt1 were examined by immunoprecipitation and western blot. Results: Our study showed that RSV treatment significantly attenuated renal injury including extracellular matrix deposition and tubulointerstitium damage. Renal cortical mRNA levels of ICAM-1, TNF-a, and TGF-b, protein expression of fibronectin and Smad3 acetylation were significantly upregulated in the UUO group. However, treatment with RSV significantly decreased the expression of these proteins. Furthermore, RSV also decreased the levels of reactive oxygen species (ROS) including MDA and 8-OHdG, and increased the level of SOD, which protects cells against ROS damage. Conclusion: Our findings suggest that RSV treatment inhibits oxidative stress, Smad3 acetylation, and renal interstitial fibrosis. Therefore, RSV may have potential as a therapeutic target for the treatment of chronic kidney disease.

Inadequate oxygen supply is probably one of the most important pathophysiological mechanisms of cardiomyocyte damage in ischemic heart disease. Tetramethylpyrazine (TMP, also known as ligustrazine) is the main active ingredient isolated from the rhizome of Ligusticum chuanxiong Hort. A previous study reported that the TMP could exert cardioprotective activity. This study aimed to explore the molecular mechanism of the protective effects of TMP on cardiomyocyte damage caused by hypoxia. The viability and apoptosis of cardiomyocytes H9c2 were detected using cell counting kit‐8 assay and annexin V‐FITC/PI staining, respectively. Quantitative reverse transcription polymerase chain reaction was conducted to measure the expression level of microRNA‐449a (miR‐449a). Cell transfection was performed to upregulate the expression level of miR‐449a or downregulate the expression level of sirtuin 1 (Sirt1). The protein expression levels of Sirt1 and key factors involved in cell apoptosis and phosphatidylinositol 3‐kinase/protein kinase 3 (PI3K/AKT) pathway were evaluated using western blot analysis. We found that the hypoxia incubation inhibited H9c2 viability, induced cell apoptosis, and inactivated the PI3K/AKT pathway. TMP treatment partially relieved the hypoxia‐caused H9c2 cell viability loss and apoptosis, as well as reversed the hypoxia‐caused inactivation of the PI3K/AKT pathway. Moreover, TMP partially alleviated the upregulation of miR‐449a in H9c2 cells caused by hypoxia. Overexpression of miR‐449a weakened the effects of TMP on hypoxia‐treated H9c2 cells. Furthermore, Sirt1 was a target gene of miR‐449a. Knockdown of Sirt1 also weakened the effects of TMP on hypoxia‐treated H9c2 cells. In conclusion, TMP partially relieved hypoxia‐caused cardiomyocytes H9c2 viability loss and apoptosis at least through downregulating miR‐499a, upregulating Sirt1, and then activating the PI3K/AKT pathway.

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Valvulopathy is a familiar heart disease, which fearfully harms the health of the body. We studied the effects and mechanism of long noncoding RNA maternally expressed gene 3 (lncMEG3) on MVICs cell in inflammatory damage. Cell Counting Kit‐8 and flow cytometry were respectively used to detect the effect of tumor necrosis factor α (TNF‐α), MEG3 and microRNA (miR)‐101a on cell viability and apoptosis. Moreover, MEG3 and miR‐101a expression were changed by cell transfection and investigated by reverse transcription‐quantitative polymerase chain reaction. Furthermore, Western blot was used to investigate the levels of Bax, pro‐caspase‐3, cleaved‐caspase‐3, pro‐caspase‐9, cleaved‐caspase‐9, interleukin (IL)‐1β, IL‐6 and related‐proteins of cell pathways. Otherwise, the levels of IL‐1β and IL‐6 were also investigated by enzyme‐linked immunosorbent assay kit. Reactive oxygen species (ROS) was examined by ROS assay. We found TNF‐α caused inflammatory damage and upregulated MEG3. MEG3 was overexpressed and silenced in cells. Besides, MEG3 deteriorated inflammatory damage. Furthermore, MEG3 negatively regulated miR‐101a and miR‐101a mimic could reverse the effect of pc‐MEG3. Besides, MEG3 enhanced the JNK and NF‐κB pathways by downregulating miR‐101a. In conclusion, MEG3 deteriorated cell inflammatory damage by downregulating miR‐101a via JNK and NF‐κB pathways.

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