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Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced Cirrhotic Rats

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Abstract

Objective

To evaluate the preventive effect of salvianolate (Sal B) on glucose metabolism disorders of dimethylnitrosamine (DMN)-induced cirrhotic rats.

Methods

Fifty-five Wistar rats were randomly divided into a control group (n=10) and a cirrhotic group (n=45) according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups (n=15), respectively. Rats in the model group were given saline, two treatment groups were given Sal B (50 mg/kg), metformin (150 mg/kg) respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test (OGTT), and fasting plasma glucose (FPG), fasting insulin (FINS), hepatic glycogen, hydroxyproline (HYP) and liver function were detected at the end of the treatment. Area under the curve (AUC) for OGTT was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining (HE), Sirius Red staining and Masson’s trichrome staining, respectively. Hepatic expression of α-smooth muscle actin (α-SMA) and collagen (Col I) were evaluated by immunohistochemical staining.

Results

Compared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate (GIR), FPG, FINS levels and hepatic glycogen at the end of administration (P<0.05 or P<0.01). Meanwhile, Sal B significantly decreased AUC for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level (P<0.05 or P<0.01). Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of α-SMA and Col I in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis (P<0.05). Metformin increased insulin sensitivity more potently than Sal B (P<0.05).

Conclusions

Sal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.

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Authors and Affiliations

  1. Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Li-rui Tang, Yan-yan Tao & Cheng-hai Liu

  2. Department of Emergency Medicine, Putuo Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China

    Li-rui Tang

  3. Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai, 201203, China

    Cheng-hai Liu & Hai-nan Wang

  4. E-Institute of Traditional Chinese Medicine Internal Medicine, Shanghai Municipal Education Commission, Shanghai, 201203, China

    Cheng-hai Liu

  5. China Food and Drug Administration, Beijing, 100053, China

    Hai-nan Wang

Authors
  1. Li-rui Tang
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  2. Yan-yan Tao
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  3. Cheng-hai Liu
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Corresponding author

Correspondence to Hai-nan Wang.

Additional information

Supported by the National Science and Technology Major Project (No. 2014ZX10005001) and the International S&T Cooperation Program of China (No. 2014DFA31440), “Three Year Action Plan” for Development of Traditional Chinese Medicine in Shanghai (No. ZY3CCCX-2-1003), Shanghai Clinical Key Laboratory of Traditional Chinese Medicine (No.14DZ2273200)

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Tang, Lr., Tao, Yy., Liu, Ch. et al. Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced Cirrhotic Rats. Chin. J. Integr. Med. 24, 661–669 (2018). https://doi.org/10.1007/s11655-017-2773-5

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  • DOI: https://doi.org/10.1007/s11655-017-2773-5

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