Myricetin attenuates renal fibrosis by activating Nrf2/HO-1 pathway to inhibit oxidative stress / 药学学报

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL-1) were used to induce fibrotic model, and high glucose (30 mmol·L-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Protective effects of Baicalin on intestinal mucosa injury by inhibiting nuclear factor-κB expression in rats with partial common bile duct ligation / 中华实用儿科临床杂志

Objective To investigate the effects of Baicalin on intestinal mucosal injury in rats with partial common bile duct ligation (PCBDL).Methods Forty male Wistar rats were randomly divided into 4 groups equally:sham operation,PCBDL,PCBDL1 and PCBDL2.Rats in PCBDL,PCBDL1 and PCBDL2 groups were subjected to partial common bile duct ligation.Baicalin [80 mg/(kg · d)] was fed in PCBDL1 group (for 2 weeks) and PCBDL2 group (for 3 weeks),while for other groups,9 g/L saline in the same volume was fed.Ileum mucosa were prepared for microscopic examination.The intestinal mucosal injury in rats was observed and scored.The level of NF-κB mRNA expression by Fluorescent in Situ Hybridization,and the level of NF-κB protein were determined by immunohistochemistry.Results 1.Compared with PCBDL group (3.2 ± 0.5),the pathological severity scores of intestinal mucosa significantly declined (F =21.120,P ＜ 0.01) in PCBDL1 group (1.9 ± 0.2) and PCBDL2 group (1.5 ± 0.3).2.Compared with sham operation group(0.066 ± 0.006),PCBDL1 group (0.107 ± 0.011),and PCBDL2 group (0.098 ± 0.010),NF-κB expression in PCBDL group (0.155 ± 0.012) presented significantly up-regulation (F =76.8,P ＜ 0.01).3.Compared with sham operation,PCBDL1 group,and PCBDL2 group,the positive expression rates of NF-κB mRNA of intestinal mucosal epithelium in PCBDL group significantly increased.Conclusions It is suggested that Baicalin exert protective effects on the intestinal mucosal injury in rats with PCBDL,partially by inhibiting NF-κB mRNA,down-regulating NF-κB protein expression of intestinal mucosal epithelial cells.

Ultrastructural Changes of the Bile Canaliculi after Common Bile Duct Ligation

The purpose of this study was to investigate the morphologic changes of the bile canaliculi and its associated structures of the liver induced by common bile duct ligation(CBDL) in the rat. The canalicular surface and lateral surface of the dry-fractured hepatocytes was studied with scanning electron microscopy at 1~6 weeks post ligation. The first week after CBDL, the bile canaliculi were dilated. The microvilli were increased in number and the lumens contained granular materials After 2 weeks or more, the bile canaliculi were dilated to a variable degree, and with irregularity, measuring from 1.5 to 5 micrometer in diameter, and in the advanced stage, the canaliculi showed blunting and the disappearance of microvilli. Some canaliculi had sprouting side branches. At 4~6 weeks post-ligation, the lateral surface of the hepatocytes also showed some irregularity and a tortuous appearance, and numerous small sized microvillous projections were formed. The tubular structures of the proliferated SER distributed adjacent to the lateral surface of the hepatocytes, and the direct connection of a tubular structure and the cytoplasmic membrane was observed. These results suggest that the deformity and loss of microvilli of bile canaliculi reflect the disturbance of bile secretion from the hepatocytes. And prolonged obstruction of bile flow may result in bile excretion via the lateral surface of hepatocytes.

Left ventricular responses during iigation of common bile duct and pulling gallbladder / 中华麻醉学杂志

The experiment was undertaken to investigate the influences of ligation of the common bile duct (CBD) and pulling the gallbladder on the left ventricular function. Fourteen rabbits served as the subjects with the CBD being tied off. The cathter was inserted into the left ventricle to measure left ventricular stroke pressure (LVSP) and?dp/dt, which were recorded before and 5 days after the ligation of CBD respectively. The results showed that the value of +dp/dt decreased significantly (P0.05); LVSP, SP, HR and the values of ?dp/dt reduced markedly immediately after the gallbladder being pulled (P

The Effect of Common Bile Duct Ligation on Liver Morphology and Coper Metabolism in Rat

To clarity the effect of biliary obliteration on copper metabolism of rat liver and on the hepatic morphology, 0.5% cuppuric sulfate was administered intraperitoneally for 42 days following ligation of the common bile duct (CBD) of Sprague-Dawley rats. The blood copper concentration, the hepatic copper content and the accumulation patterns of copper and copper binding protein in the liver were examined and compared with those of the simple CBD ligation group and the simple copper over loaded group. CBD ligation induced marked proliferation of bile ductular structures which, after expanding the portal tracts, invaded and divided the hepatic lobules. There was, however, no excess fibosis beyond what needed to support the new ductules. The blood copper concentration and the hepatic copper content were increased by copper overload with or without CBD ligation, particularly incases with CBD ligation. Liver cell necrosis did not occur by the overloaded copper alone in rats. The hepatic copper and copper binding protein were accumulated at periportal liver cells in the group of coppe overload after CBD ligatio, whereas they began to appear at perivenular hepatocytes in the simple copper overloaded group. In conclusion, it is suggested that CBD ligation does not induce excess fibrosis or liver cirrhosis in rat as far as during our experimental period, but affect significantly on copper metabolism by intrahepatic redistribution of the copper and the copper binding proteins.