Blockage of UCHL1 activity attenuates cardiac remodeling in spontaneously hypertensive rats.

Cardiac remodeling is an important pathological process ultimately leading to heart failure. Ubiquitin carboxy-terminal hydrolase 1 (UCHL1) is a deubiquitinase that plays a critical role in neurodegenerative diseases and cancer. However, its role in cardiac remodeling in spontaneously hypertensive rats remains unclear. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were administered the UCHL1 inhibitor LDN-57444 (20 µg/kg/day) from 2 months of age for 4 months. Blood pressure, cardiac hypertrophy, fibrosis, inflammation, and oxidative stress were evaluated by the tail-cuff system, echocardiography, and histological analysis. Gene and protein expression levels were examined by real-time PCR and immunoblotting analysis. At 6 months of age, the expression of UCHL at the mRNA and protein levels was significantly upregulated in SHRs compared with WKYs. Moreover, systolic blood pressure, cardiac performance, left ventricular (LV) hypertrophy, fibrosis, inflammation, and superoxide production were significantly increased in SHRs compared with WKYs, and these effects were markedly attenuated by LDN-57444 after 4 months of administration. These beneficial actions were possibly associated with a reduction in blood pressure and inactivation of multiple signaling pathways, including AKT, ERK1/2, STAT3, calcineurin A, TGF-ß/Smad2/3, and NF-κB. In conclusion, the results indicate that UCHL1 is involved in hypertensive cardiac remodeling in SHRs, and targeting UCHL1 activity may be a novel potential therapeutic approach for the treatment of hypertensive heart diseases.

Effect of Huangqisan on Endoplasmic Reticulum Stress Signaling Pathway in Liver Tissues of High-fat Diet-induced Obese Rats / 中国实验方剂学杂志

Objective: To explore the effect of Huangqisan on endoplasmic reticulum stress signaling pathway in liver tissues of high-fat diet-induced obese rats and its mechanisms. Method: Male SD rats were selected and fed with high-fat diet for 7 weeks continuously to establish an obese rat model. Then, the rats were randomly divided into model group, low and high-dose Huangqisan group (1.2, 2.4 g·kg-1), and Lipitor group (2 mg·kg-1), and orally administered with drugs for 15 consecutive weeks. The control group and the model group were perfused with the same volume of normal saline. The body weight, epididymal fat coefficient and liver coefficient of each group were determined separately. Fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were determined by biochemical reagent method. The epididymal visceral adipose tissue and liver pathological changes were observed by hematoxylin and eosin (HE) staining. And the protein expression levels of sterol regulation element-binding transcription factor 1 (SREBP-1c), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1α), p-inositol requiring enzyme 1 (p-IRE1α) in liver tissues were detected by Western blot methods. Result: Compared with the control group, the body weight, epididymal fat coefficient and liver coefficient of the model group were significantly increased(PPPα/p-IRE1α were increased(PPPPα/p-IRE1α protein expression levels to different degrees(PPConclusion: Huangqisan could regulate the glucose and lipid metabolism, alleviate liver pathology and reduce body weight, and its mechanism was probably related to reduction of SREBP-1c, PERK, IRE1α/p-IRE1α proteins expression levels.

Anti-fibrotic effects of the Masson pine pollen aqueous extract on hepatic fibrosis rat model.

AIM: To observe the antifibrotic effects of Masson Pine Pollen aqueous extract. METHODS: Adult Sprague-Dawley rats were randomly divided into control (CG), hepatic fibrosis model (MG), MPPAE low dose (LG), MPPAE high dose (HG), and MPP original powder (MPPOP; OG) groups. Each group was treated with specific protocols and sacrificed 8 weeks later. Multiple indicators such as serum transaminase, HE staining of the liver tissue, and relevant indexes to fibrosis were determined. RESULTS: Severe hyperplasia of fibrous connective tissues was observed in livers of the MG group rats, while aspartate transaminase and alanine transaminase levels and collagen content obviously increased, superoxide dismutase and glutathione peroxidase activities and MMPs expression decreased, malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine concentrations increased, while mRNA expressions of hepatic stellate cell (HSC)-related cytokines such as transforming growth factor-ß1 and platelet-derived growth factor, transcription factors such as nuclear factor-κB p65, and signaling protein α-smooth muscle actin were all increased significantly. CONCLUSIONS: MPPAE effectively inhibited the fibrotic process in this CCl4-induced hepatic fibrosis rat model. It may be associated with synergic functions of antioxidant activity, inhibitory activity on HSC proliferation, collagen synthesis, and MMPs expression induction.

[Effects of zinc supplementation on zinc and calcium levels in serum and tissue in burned rats].

OBJECTIVE: To explore the effects of zinc supplementation on zinc and calcium levels in serum and tissue in burned rats. METHODS: Eighty SD rats were randomly divided into C group (control group without scald, n = 8), and N, W, H groups (each consisting of 24 rats), in which the rats were exposed to scalding resulting in partial thickness burns covering 15% of the total body surface area on the back, and then they were fed with diets containing zinc 40 microg/g in N and W groups, and 80 microg/g in H group. A cream containing zinc 761.1 microg/g was applied on the wound in W group at the same time. Eight rats of each group were sacrificed on day 1, 3 and 7 after scald respectively. Venous blood and samples of liver, femur and scald skin were harvested. Zinc and calcium contents in serum and tissues were determined with atomic absorption spectrophotometer. RESULTS: The serum Zn(2+) levels in N, W groups were lower than C group, however, it was obviously higher in H group (up to 16.2 micromol/L) on day 1 after scald. The liver Zn(2+) showed an increasing tendency in all groups, while Ca(2+) level declined in H group, but increased in N, W group. The bone Zn(2+) and Ca(2+) levels showed a progressive declination in all groups from day 1 to 7 after scald. The changes were more obviously in N group than H group (P < 0.05). The Zn(2+) content of the scalded skin increased obviously in H group on first day after scald and in W group on 7th day after scald. The Ca(2+) contents of scalded skin showed marked increases in all groups, especially in N group, but least in W group. CONCLUSION: There are obvious changes in Zn(2+) and Ca(2+) contents of serum and tissues after scald injury and zinc supplementation. The effects of zinc supplementation on calcium level in the tissue need to be further studied.